Sample records for routine toxicity screening

Cytomegalovirus (CMV) screening during pregnancy has been widely discussed for several years, but still no consensus has been agreed. With a number of live births of 750,000 per year in France, we would expect 7500 infected infants at birth per year (rate of congenital infection of 1%). Among infected infants at birth, the number of severely infected foetuses would be approximately 75, the number of infants with severe sequelae would be 480, 675 approximately would present with hearing loss and the number of asymptomatic infants would be 6270. Five different preventive methods for congenital CMV infection are possible: (1) Routine CMV screening at the beginning of pregnancy for primary prevention. (2) Secondary prevention by antenatal diagnosis of congenital CMV infection complications. (3) Tertiary prevention by serological testing during pregnancy. (4) Tertiary prevention by serological screening at birth. (5) Tertiary prevention: Hearing loss screening at birth. The aims of this review are to define the advantages and disadvantages of these different methods of CMV screening during pregnancy and to determine if the current available information would make systematic testing acceptable.

Fischer's method for rapid detection of acute iron toxicity is modified to suit pediatric cases. TPTZ (2,4,6-tripyridyl-s-triazine) is the chromogen of choice since in a small volume of serum slight to moderate hemolysis can cause a false positive result bathophenanthroline. Ordinary labware is amenable to this simplified procedure.

Case report on a severe cardial malformation associated with trisomia 21, diagnosed by ultrasound-screening in the 34th week of gestation. Further diagnostic evaluation of the case and therapeutic management are described. The problems of modern malformation diagnostics by routine ultrasound scanning in pregnancy are discussed.

Routine second screening of most newborns at 8–14 days of life for a panel of newborn conditions occurs in 12 U.S. states, while newborns in the other states typically undergo only a single routine newborn screen. The study objective was to evaluate screening consequences for primary congenital hypothyroidism (CH) in one- and two-screen states according to laboratory practices and medical or biochemical characteristics of screen-positive cases. Individual-level medical and biochemical data were retrospectively collected and analyzed for 2,251 primary CH cases in one-screen (CA, WI) and two-screen (AL, DE, MD, OR, TX) states. Aggregate data were collected and analyzed for medical and biochemical characteristics of all screened newborns in the states. Among the states evaluated in this study, the detection rate of primary CH was higher in the one-screen states. In the two-screen states, 11.5% of cases were detected on the second screen. In multivariate analyses, only race/ethnicity was a significant predictor of cases identified on the first versus second screen, which likely reflects a physiologic difference in primary CH presentation. Newborn screening programs must heed the potential for newborns with CH not being detected by a single screen, particularly newborns of certain races/ethnicities. If the two-screen states converted to a single screen using their current algorithms, newborns currently identified on the routine second screen would presumably not be detected, resulting in probable delayed diagnosis and treatment. However, based on the one-screen state experiences, with appropriate modifications in screening method and algorithm, the two-screen states might convert to single screen operation for CH without loss in performance. PMID:26293295

Intimate partner violence (IPV) is a significant public health issue affecting around 3 million U.S. women during their lifetimes; this paper provides guidance to policymakers on addressing IPV. In 2011, an Institute of Medicine panel recommended routine IPV screening for women and adolescents as part of comprehensive preventive care services, which is in conflict with the 2004 U.S. Preventive Services Task Force recommendations. The current evidence base for policymaking suffers weaknesses related to study design which should be addressed in future research. Meanwhile, policymakers should consider available evidence in their settings, assess local needs, and make recommendations where appropriate. PMID:25011677

Background and Objective: A routine chest radiograph is mandatory in many institutions as a part of pre-employment screening. The usefulness of this has been studied over the years keeping in mind the added time, cost, and radiation concerns. Studies conducted outside India have shown different results, some for and some against it. To our knowledge, there is no published data from India on this issue. Materials and Methods: A retrospective review of the reports of 4113 pre-employment chest radiographs done between 2007 and 2009 was conducted. Results: Out of 4113 radiographs, 24 (0.58%) candidates required further evaluation based on findings from the screening chest radiograph. Out of these, 7 (0.17%) candidates required appropriate further treatment. Interpretation and Conclusions: The percentage of significant abnormalities detected which needed further medical intervention was small (0.17%). Although the individual radiation exposure is very small, the large numbers done nation-wide would significantly add to the community radiation, with added significant cost and time implications. We believe that pre-employment chest radiographs should be restricted to candidates in whom there is relevant history and/or clinical findings suggestive of cardiopulmonary disease. PMID:27857470

To assess nanomaterial vertebrate toxicity, a high-content screening assay was created using developing zebrafish, Danio rerio. This included a diverse group of nanomaterials (n=42 total) ranging from metallic (Ag, Au) and metal oxide (CeO2, CuO, TiO2, ZnO) nanoparticles, to non...

... birth not useful for routinescreening of first-time pregnancies Skip sharing on social media links Share ... hold promise in predicting preterm delivery in first-time pregnancies identified only a small proportion of cases ...

The case for routine human immunodeficiency virus (HIV) screening of all couples seeking assisted reproductive treatment is so strong that it should be made obligatory for all couples entering IVF programmes to be given information about HIV transmission, and offered testing. In August 1999, questionnaires regarding routine HIV screening of couples seeking IVF treatment were sent to the medical directors of the 74 licensed assisted conception units in the UK. Of the 45 (60.8%) centres who responded, 19 (42.2%) routinelyscreen both partners for HIV antibodies, 25 (55.5%) do not screen and one centre selectively screens high-risk patients. There was no significant difference in the proportion of centres that routinely carried out screening with regards to the unit size: six out of 13 (46.2%) small units compared with 13/32 (40.6%) large units. In all, 17 centres (37.8%) rated HIV screening as essential, nine (20%) as desirable, 11 (24.4%) as not required, while eight (17. 8%) centres did not comment. Of the 19 centres that have a routinescreening policy, 18 have management protocols in the event that the test is positive. Of these 18 centres, 12 adhere rigidly to the protocol, while five centres adhere to the protocol with few exceptions and the remaining one uses its protocol for guidance only. The main reasons for not employing routine HIV screening were: the lack of cost effectiveness, low prevalence of HIV infection in their population, necessity for and cost of counselling, uncertainty about the need for screening and potential delay to start of treatment.

This study was conducted to determine whether newborns from different ethnic and socioeconomic groups in Washington State are equally likely to have a routine second newborn screening (NBS) test and if there are identifiable factors associated with not having a second test. For many years, the standard of care for NBS in Washington has been that newborns should receive a routine second screening test at age 7-10 days. However, data collected by State Department of Health (DOH) staff for the past several years indicated that only about 80% of newborns receive a routine second NBS test. The data presented here suggest that identifiable factors (i.e., barriers) exist in accessing a routine second NBS test in Washington. Increased educational efforts targeting certain high-risk infants, their parent/caretakers, and primary care providers are apparently needed to ensure equal access to a routine second test.

We are far from having seen the ideal method of screening for colorectal cancer (CRC) and the downsides of screening have not been fully addressed. Funding of adequately sized screening trials with a 10-15-year perspective for endpoints CRC mortality and incidence is difficult to get. Also, with such time horizons, there will always be an ongoing study to be awaited before feeling obliged to invest in the next. New, promising screening methods may, however, emerge far more often than every 10th year, and the knowledge gap may easily widen unless research is made a key responsibility for any ongoing cancer screening program. Previous lost battles on screening research may be won if accepting that scientific evidence may be obtained within the framework of screening programs - provided that they are designed as platforms for Comparative Effectiveness Research (CER). Accepting that CER-based screening programs should be preferred to non-CER programs and seriously compete for their funding sources, then CER screening programs may not be considered so much as contenders for ordinary clinical research funds. Also, CER within a screening framework may benefit patients in routine clinics as shown by screening research in Nordic countries. The Nordic countries have been early contributors to research on CRC screening, but slow in implementing screening programs.

Objective CDC has recommended routine HIV screening since 2006. However, few community health centers (CHCs) routinely offer HIV screening. Research is needed to understand how to implement routine HIV screening programs, particularly in medically underserved neighborhoods with high rates of HIV infection. A routine HIV screening program was implemented and evaluated in a Philadelphia, Pennsylvania, neighborhood with high rates of HIV infection. Methods Implementation science is the study of methods to promote the integration of research findings and evidence into health-care policy and practice. Using an implementation science approach, the results of the program were evaluated by measuring acceptability, adoption, and penetration of routine HIV screening. Results A total of 5,878 individuals were screened during the program. HIV screening was highly accepted among clinic patients. In an initial needs assessment of 516 patients, 362 (70.2%) patients reported that they would accept testing if offered. Routinescreening policies were adopted clinic-wide. Staff trainings, new electronic medical records that prompted staff members to offer screening and evaluate screening rates, and other continuing quality-improvement policies helped promote screenings. HIV screening offer rates improved from an estimated 5.0% of eligible patients at baseline in March 2012 to an estimated 59.3% of eligible patients in December 2014. However, only 5,878 of 13,827 (42.5%) patients who were offered screening accepted it, culminating in a 25.2% overall screening rate. Seventeen of the 5,878 patients tested positive, for a seropositivity rate of 0.3%. Conclusion Routine HIV screening at CHCs in neighborhoods with high rates of HIV infection is feasible. Routinescreening is an important tool to improve HIV care continuum outcomes and to address racial and geographic disparities in HIV infection. PMID:26862228

Short-term whole effluent toxicity testing, which is currently a requirement of the U.S. EPA`s National Pollution Discharge Elimination System (NPDES), commonly uses the cladoceran species Ceriodaphnia dubia. Despite the advantages to using a common test species to model the toxic effects of effluents, it could be argued that toxicity test results would be more meaningful if a wider variety of test organisms were commonly used. One particular argument against C. dubia is that tests conducted with this species do not always reflect local, site-specific conditions. The careful selection and use of an indigenous test species would produce a more realistic model of local instream effects and would account for regional differences in water quality. Permitted effluent discharges from Savannah River Site (SRS), a government weapons facility operated by the U.S. Department of Energy, require toxicity testing with C. dubia. However, water quality in these receiving streams is markedly different (lower pH and hardness) from standard laboratory water used for the culturing and testing of C. dubia, and it has been shown that this receiving water presents varying degrees of toxicity to C. dubia. Based on these results, it is possible that toxic effects observed during an effluent study could be the result of test organism stress from the dilution water and not the effects of SRS effluents. Therefore, this study addressed the substitution of C. dubia with an indigenous cladoceran species, Daphnia ambigua for routine regulatory testing at SRS. Given the indigenous nature of this species, combined with the fact that it has been successfully cultured by other investigators, D. ambigua was ideal for consideration as a replacement for C. dubia, but further study of the overall success and sensitivity of laboratory-reared D. ambigua was required. This investigation determined that D. ambigua could be laboratory cultured with only minimal changes to established regulatory protocol and

Since 2006, numerous testing initiatives have been launched across the United States to increase the number of individuals who know their HIV status. These initiatives are often venue based and reported in a variety of settings. However, the effectiveness of these initiatives has not been evaluated to determine if patients were identified earlier in the course of disease or would not have been otherwise tested. In 2010, a publicly funded teaching hospital implemented an electronic medical record prompt to improve the rate of routine HIV screening and diagnosis, focusing on primary care office visits. Both sex and CD4 count were found to be significantly related to being newly diagnosed after the intervention. Routine testing in primary care is an effective strategy to diagnose patients earlier in disease progression, particularly men who might otherwise not be tested and thus would remain undiagnosed until developing symptoms from advanced disease.

An inexpensive apparatus was fabricated to monitor and record changes in the motility patterns of small aquatic invertebrates, such as Artemia salina and Daphnia magna, during acute toxicity tests. Within hours of exposure to a range toxicant concentrations the motility patterns change in a way that predicts the EC50. The work to date suggests there is a correlation between the EC50 following a 60 hour exposure, and motility data collected within the first 40 minutes of the test. The apparatus may be useful to speed range finding tests and for shortening the duration of acute toxicity tests of an effluent or receiving water. The apparatus may also be used to quantify erratic swimming in surviving organisms when a test is terminated.

Purpose: The purpose of this study was to report the spectrum of anterior and posterior segment diagnoses in Asian Indian premature infants detected serendipitously during routine retinopathy of prematurity (ROP) screening during a 1 year period. Methods: A retrospective review of all Retcam (Clarity MSI, USA) imaging sessions during the year 2011 performed on infants born either <2001 g at birth and/or <34.1 weeks of gestation recruited for ROP screening was performed. All infants had a minimum of seven images at each session, which included the dilated anterior segment, disc, and macula center and the four quadrants using the 130° lens. Results: Of the 8954 imaging sessions of 1450 new infants recruited in 2011, there were 111 (7.66%) with a diagnosis other than ROP. Anterior segment diagnoses seen in 31 (27.9%) cases included clinically significant cataract, lid abnormalities, anophthalmos, microphthalmos, and corneal diseases. Posterior segment diagnoses in 80 (72.1%) cases included retinal hemorrhages, cherry red spots, and neonatal uveitis of infective etiologies. Of the 111 cases, 15 (13.5%) underwent surgical procedures and 24 (21.6%) underwent medical procedures; importantly, two eyes with retinoblastoma were detected which were managed timely. Conclusions: This study emphasizes the importance of ocular digital imaging in premature infants. Visually significant, potentially life-threatening, and even treatable conditions were detected serendipitously during routine ROP screening that may be missed or detected late otherwise. This pilot data may be used to advocate for a possible universal infant eye screening program using digital imaging. PMID:26139795

Purpose Patients with idiopathic clubfoot are considered at increased risk for having developmental dysplasia of the hips (DDH). However, the studies showing this association have been relatively small. Many clinicians who treat idiopathic clubfoot routinelyscreen the hips of these patients with ultrasound or radiograph due to the concerns of increased risk of DDH. We evaluated a large clubfoot population to determine the risk of DDH and compare this to a population of children without clubfoot. We also evaluated if the clubfoot patients found to have DDH would have been discovered by standard DDH screening. Methods We identified infants in three states (MA, NY, NC) who were reported to each state’s birth defects registry as having a clubfoot. A second cohort of infants without clubfoot was also identified as a control group. Mothers of these children were contacted to be included in the study, and a computer-assisted telephone interview was administered by one of the study nurses, including questions about treatment of DDH. The child’s median age at interview was 7 months. Mothers of clubfoot cases were also contacted for follow-up at mean age of 3.3 years. Results Families of 677 patients with clubfoot and 2037 controls were interviewed. 5/677 (0.74%) patients with clubfoot and 5/2037 (0.25%) controls reported having their infant treated with a brace or harness for hip problems (p=0.134). Of the patients with clubfoot, two of them did not need treatment for their DDH and two would have been discovered by standard hip screening. Follow-up study at 3.3 years of age found no serious late hip dysplasia. Conclusions Treatment of DDH was uncommon in all children; the higher proportion in infants with clubfoot was not statistically different than controls. Of the patients with clubfoot and DDH, standard hip screening would have been appropriate and others did not need treatment. These data suggest that routine hip ultrasound or radiographic screening of idiopathic

Toxicological analysis is indispensable in forensic autopsy laboratories, but often depends on the limitations of individual institutions. The present study reviewed routine drug screening data of forensic autopsy cases (n=2996) during an 18.5-year period (January 1996-June 2014) at our institute to examine the efficacy of the procedures and findings in autopsy diagnosis and interpretation. Drug screening was performed using on-site immunoassay screening devices and gas chromatography/mass spectrometry (GC/MS) in all cases, followed by re-examination using GC/MS and liquid chromatography/tandem mass spectrometry (LC/MS/MS) at a cooperating institute in specific cases in the last 4 years. GC/MS detected drugs in 486 cases (16.2%), including amphetamines (n=160), major tranquilizers (n=72), minor tranquilizers (n=294), antidepressants (n=21), cold remedies (n=77), and other drugs (n=19). Among these cases, fatal intoxication (n=123) involved amphetamines (n=73), major tranquilizers (n=37), minor tranquilizers (n=86), antidepressants (n=3), and cold remedies (n=9); most cases involved self-administration, alleged suicide and accidental overdose, while homicide was not included. These drugs were also identified in other manners of death, including homicide (n=40/372), suicide (n=34/226), accidental falls (n=27/129), and natural death (n=72/514). In these cases, on-site immunoassay screening of drugs of abuse showed negative findings in 2440 cases (81.4% in all cases), while GC/MS detected other drugs in 218 cases (7.3% in all cases), including several antipsychotic drugs, acetaminophen and salicylic acid. Further analysis using LC/MS/MS detected low concentrations of benzodiazepines in 32 cases, and also anti-diabetic and hypertensive drugs in a case of fatal abuse. These observations indicate the efficacy of systematic routine toxicological analysis to investigate not only the cause of death but also the background of fatalities in forensic autopsy. The provision of

Mine tailings piles and abandoned mine soils are often contaminated by a suite of toxic metals, which were released in the mining process. Traditionally, toxicity of such areas has been determined by numerous chemical methods including the Toxicity Characteristic Leachate Procedure (TCLP) and traditional toxicity tests using organisms such as the cladoceran Ceriodaphnia dubia. Such tests can be expensive and time-consuming. Enzymatic bioassays may provide an easier, less costly, and more time-effective toxicityscreening procedure for mine tailings and abandoned mine soil leachates. This study evaluated the commercially available MetPLATE™ enzymatic toxicity assay test kit. The MetPLATE™ assay uses a modified strain of Escherichia coli bacteria as the test organism. Toxicity is defined by the activity of β-galactosidase enzyme which is monitored colorometrically with a 96-well spectrophotometer. The study used water samples collected from North Fork Clear Creek, a mining influenced water (MIW) located in Colorado. A great benefit to using the MetPLATE™ assay over the TCLP is that it shows actual toxicity of a sample by taking into account the bioavailability of the toxicants rather than simply measuring the metal concentration present. Benefits of the MetPLATE™ assay over the use of C. dubia include greatly reduced time for the testing process (∼2 hours), a more continuous variable due to a greater number of organisms present in each sample (100,000+), and the elimination of need to maintain a culture of organisms at all times.

Treponema pallidum infections can have severe complications if not diagnosed and treated at an early stage. Screening and diagnosis of syphilis require assays with high specificity and sensitivity. The Elecsys Syphilis assay is an automated treponemal immunoassay for the detection of antibodies against T. pallidum. The performance of this assay was investigated previously in a multicenter study. The current study expands on that evaluation in a variety of diagnostic settings and patient populations, at seven independent laboratories. The samples included routine diagnostic samples, blood donation samples, samples from patients with confirmed HIV infections, samples from living organ or bone marrow donors, and banked samples, including samples previously confirmed as syphilis positive. This study also investigated the seroconversion sensitivity of the assay. With a total of 1,965 syphilis-negative routine diagnostic samples and 5,792 syphilis-negative samples collected from blood donations, the Elecsys Syphilis assay had specificity values of 99.85% and 99.86%, respectively. With 333 samples previously identified as syphilis positive, the sensitivity was 100% regardless of disease stage. The assay also showed 100% sensitivity and specificity with samples from 69 patients coinfected with HIV. The Elecsys Syphilis assay detected infection in the same bleed or earlier, compared with comparator assays, in a set of sequential samples from a patient with primary syphilis. In archived serial blood samples collected from 14 patients with direct diagnoses of primary syphilis, the Elecsys Syphilis assay detected T. pallidum antibodies for 3 patients for whom antibodies were not detected with the Architect Syphilis TP assay, indicating a trend for earlier detection of infection, which may have the potential to shorten the time between infection and reactive screening test results. PMID:27358468

Purpose Routinescreening for evidence of DNA mismatch repair abnormalities can identify colorectal cancer patients with Lynch syndrome, but impact in usual care settings requires study. After implementing routinescreening at our university and safety-net health systems as usual practice, our aims were to determine outcomes, including screening process quality. Methods We conducted a retrospective cohort study from 1 May 2010 to 1 May 2011. Screening included reflexive immunohistochemistry to evaluate DNA mismatch repair protein expression for patients with colorectal cancer aged ≤70 years, with a cancer genetics team following up results. Screening outcomes, as well as challenges to a high-quality screening process were evaluated. Results We included 129 patients (mean age 56 years, 36% female); 100 had immunohistochemistry screening completed. Twelve patients had abnormal immunohistochemistry: four with definite Lynch syndrome, four with probable Lynch syndrome, and three without Lynch syndrome; one patient had an incomplete work-up. Lynch syndrome was confirmed for 6/13 asymptomatic relatives tested. Screening process quality was optimal for 77.5% of patients. Barriers to optimal quality screening included ensuring reflexive immunohistochemistry completion, complete follow-up of abnormal immunohistochemistry, and timely incorporation of results into clinical decision making. Conclusion Usual care implementation of routinescreening for Lynch syndrome can result in significant rates of detection, even in a largely safety-net setting. To optimize implementation, challenges to high-quality Lynch syndrome screening, such as ensuring reflexive screening completion and clinically indicated genetic testing and follow-up for abnormal screens, must be identified and addressed. PMID:23598716

Objective The Centers for Disease Control and Prevention has recommended emergency department (ED) opt-out HIV screening since 2006. Routinescreening can prove challenging due to the ED's complexity and competing priorities. This study examined the implementation and evolution of a routine, integrated, opt-out HIV screening program at an urban academic ED in Alabama since August 2011. Methods ED routine, opt-out HIV screening was implemented as a standard of care in September 2011. To describe the outcomes and escalation of the screening program, data analyses were performed from three separate data queries: (1) encounter-level HIV screening questionnaire and test results from September 21, 2011, through December 31, 2013; (2) test-level, fourth-generation HIV results from July 9 through December 31, 2013; and (3) daily HIV testing rates and trends from September 9, 2011, through June 30, 2014. Results Of the 46,385 HIV screening tests performed, 252 (0.5%) were confirmed to be positive. Acute HIV infection accounted for 11.8% of all HIV patients identified using the fourth-generation HIV screening assay. Seventy-six percent of confirmed HIV-positive patients had successful linkage to care. Implementation of fourth-generation HIV instrument-based testing resulted in a 15.0% decline in weekly HIV testing rates. Displacement of nursing provider HIV test offers from triage to the bedside resulted in a 31.6% decline in weekly HIV testing rates. Conclusion This program demonstrated the capacity for high-volume, routine, opt-out HIV screening. Evolving ED challenges require program monitoring and adaptation to sustain scalable HIV screening in EDs. PMID:26862235

Posttraumatic stress disorder (PTSD), anxiety, and depression are the most common mental health disorders in the refugee population. High rates of violence, trauma, and PTSD among refugee women remain unaddressed. The process of implementing a mental health screening tool among multi-ethnic, newly-arrived refugee women receiving routine obstetric and gynecologic care in a dedicated refugee women’s health clinic is described. The Refugee Health Screener-15 (RHS-15) is a culturally-responsive, efficient, validated screening instrument that detects symptoms of emotional distress across diverse refugee populations and languages. An interdisciplinary community partnership was established with a local behavioral health services agency to facilitate the referral of women scoring positive on the RHS-15. Staff and provider training sessions, as well as the incorporation of bi-cultural, multi-lingual Cultural Health Navigators, greatly facilitated linguistically-appropriate care coordination for refugee women in a culturally sensitive manner. Twenty-six (23.2%) of the 112 women who completed the RHS-15 scored positive; of which 14 (53.8%) were Iraqi, one (3.8%) was Burmese, and three (11.5%) were Somali. Among these 26 women, eight (30.8%) are actively receiving mental health services, and five (19.2%) have appointments scheduled. However 13 (50%) are not enrolled in mental health care due to either declining services (46.2%), or a lack of insurance (53.8%). Screening for mental disorders among refugee women will promote greater awareness and identify those individuals who would benefit from further mental health evaluation and treatment. Sustainable interdisciplinary models of care are necessary to promote health education, dispel myths and reduce the stigma of mental health. PMID:25383999

Posttraumatic stress disorder (PTSD), anxiety, and depression are common mental health disorders in the refugee population. High rates of violence, trauma, and PTSD among refugee women remain unaddressed. The process of implementing a mental health screening tool among multiethnic, newly arrived refugee women receiving routine obstetric and gynecologic care in a dedicated refugee women's health clinic is described. The Refugee Health Screener-15 (RHS-15) is a culturally responsive, efficient, validated screening instrument that detects symptoms of emotional distress across diverse refugee populations and languages. An interdisciplinary community partnership was established with a local behavioral health services agency to facilitate the referral of women scoring positive on the RHS-15. Staff and provider training sessions, as well as the incorporation of bicultural, multilingual cultural health navigators, greatly facilitated linguistically appropriate care coordination for refugee women in a culturally sensitive manner. Twenty-six (23.2%) of the 112 women who completed the RHS-15 scored positive, of which 14 (53.8%) were Iraqi, 1 (3.8%) was Burmese, and 3 (11.5%) were Somali. Among these 26 women, 8 (30.8%) are actively receiving mental health services and 5 (19.2%) have appointments scheduled. However, 13 (50%) are not enrolled in mental health care because of either declining services (46.2%) or a lack of insurance (53.8%). Screening for mental disorders among refugee women will promote greater awareness and identify those individuals who would benefit from further mental health evaluation and treatment. Sustainable interdisciplinary models of care are necessary to promote health education, dispel myths, and reduce the stigma of mental health.

This study compared the relative sensitivity of five inexpensive, rapid toxicity tests to the sensitivity of five standard aquatic acute toxicity tests through literature review and testing. The rapid toxicity tests utilized organisms that require little culturing or handling prior to testing: a freshwater rotifer (Branchionus ccalyciflorus); brine shrimp (Artemia salina); lettuce (Lactuca sativa); and two microbial tests (Photo bacterium phosphoreum - Microtox test, and a mixture of bacterial species - the polytox test). Standard acute toxicity test species included water fleas (Daphnia magna and Ceriadaphnta dubia), green algae (Setenastrum capricarnutum), fathead minnows (Pimephalespromelas), and mysid shrimp (Mysidopsis bahia). Sensitivity comparisons between rapid and standard acute toxicity tests were based on LC5O/EC50 data from 11 test chemicals. Individually, the lettuce and rotifer tests ranked most similar in sensitivity to the standard tests, while Microtox fell just outside the range of sensitivities represented by the group of standard acute toxicity tests. The brine shrimp and Polytox tests were one or more orders of magnitude different from the standard acute toxicity tests for most compounds. The lettuce, rotifer, and Microtox tests could be used as a battery for preliminary toxicityscreening of chemicals. Further evaluation of complex real-world environmental samples is recommended.

This study compared the relative sensitivity of five inexpensive, rapid toxicity tests to the sensitivity of five standard aquatic acute toxicity tests through literature review and testing. The rapid toxicity tests utilized organisms that require little culturing or handling prior to testing: a freshwater rotifer (Branchionus calyciflorus); brine shrimp (Artemia salina); lettuce (Lactuca sativa); and two microbial tests (Photobacterium phosphoreum--Microtox{reg_sign} test, and a mixture of bacterial species--the Polytox{reg_sign} test). Standard acute toxicity test species included water fleas (Daphnia magna and Ceriodaphnia dubia), green algae (Selenastrum capricornutum), fathead minnows (Pimephales promelas), and mysid shrimp (Mysidopsis bahia). Sensitivity comparisons between rapid and standard acute toxicity tests were based on LC50/EC50 data from 11 test chemicals. Individually, the lettuce and rotifer tests ranked most similar in sensitivity to the standard tests, while Microtox fell just outside the range of sensitivities represented by the group of standard acute toxicity tests. The brine shrimp and Polytox tests were one or more orders of magnitude different from the standard acute toxicity tests for most compounds. The lettuce, rotifer, and Microtox tests could be used as a battery for preliminary toxicityscreening of chemicals. Further evaluation of complex real-world environmental samples is recommended.

Routine opt-out HIV screening is recommended for everyone between 13 and 64 years of age. An urban, academic emergency department implemented a nurse-driven routine opt-out HIV screening program. The aim of our study was to assess program uptake and opportunities to improve the program from the perspectives of emergency nurses. Emergency nurses completed a brief prediscussion questionnaire and then participated in a focus group or semi-structured one-on-one interview to elicit feedback on the routine opt-out HIV screening program. All 16 participants felt adequately prepared for the screening program. Several themes emerged from the discussions, including challenges of specific patient characteristics and overall nurse and patient support for the program. One thread across themes was the importance of good language and communication skills in such programs. While there are opportunities to improve nurse-driven routine opt-out HIV testing programs in emergency settings, this program was found to be accepted by emergency nurses.

Colonoscopy is an invaluable tool for the screening and diagnosis of many colonic diseases. For most colonoscopies, moderate sedation is used during the procedure. However, insufflation of the colon produces a nociceptive stimulus that is usually accompanied by facial grimacing/groaning while under sedation. The objective of this study was to evaluate whether a nociceptive signal elicited by colonic insufflation could be measured from the brain. Seventeen otherwise healthy patients (age 54.8 ± 9.1; 6 female) undergoing routine colonoscopy (ie, no history of significant medical conditions) were monitored using near-infrared spectroscopy (NIRS). Moderate sedation was produced using standard clinical protocols for midazolam and meperidine, titrated to effect. Near-infrared spectroscopy data captured during the procedure was analyzed offline to evaluate the brains' responses to nociceptive stimuli evoked by the insufflation events (defined by physician or observing patients' facial responses). Analysis of NIRS data revealed a specific, reproducible prefrontal cortex activity corresponding to times when patients grimaced. The pattern of the activation is similar to that previously observed during nociceptive stimuli in awake healthy individuals, suggesting that this approach may be used to evaluate brain activity evoked by nociceptive stimuli under sedation, when there is incomplete analgesia. Although some patients report recollection of procedural pain after the procedure, the effects of repeated nociceptive stimuli in surgical patients may contribute to postoperative changes including chronic pain. The results from this study indicate that NIRS may be a suitable technology for continuous nociceptive afferent monitoring in patients undergoing sedation and could have applications under sedation or anesthesia.

Free-living amoebae (FLA) are widely spread in the environment and known to cause rare but often serious infections. Besides this, FLA may serve as vehicles for bacterial pathogens. In particular, Legionella pneumophila is known to replicate within FLA thereby also gaining enhanced infectivity. Cooling towers have been the source of outbreaks of Legionnaires' disease in the past and are thus usually screened for legionellae on a routine basis, not considering, however, FLA and their vehicle function. The aim of this study was to incorporate a screening system for host amoebae into a Legionella routinescreening. A new real-time PCR-based screening system for various groups of FLA was established. Three cooling towers were screened every 2 weeks over the period of 1 year for FLA and Legionella spp., by culture and molecular methods in parallel. Altogether, 83.3 % of the cooling tower samples were positive for FLA, Acanthamoeba being the dominating genus. Interestingly, 69.7 % of the cooling tower samples were not suitable for the standard Legionella screening due to their high organic burden. In the remaining samples, positivity for Legionella spp. was 25 % by culture, but overall positivity was 50 % by molecular methods. Several amoebal isolates revealed intracellular bacteria.

Bacteria have several attributes which make them attractive as test organisms for the rapid screening of chemical pollution in natural waters. They have relatively short life cycles and, therefore, respond rapidly to environmental change. The degree of toxicity of chemicals to bacteria is normally established by measuring viability or growth. A very sensitive test has been described measuring cell multiplication inhibition of Pseudomonas putida, results being obtained after a 16 h incubation period. Because of their short generation time it is possible, however, that bacteria are capable of manifesting measurable growth within a shorter incubation period. In the present study P. putida was cultured under modified test conditions aiming at an equally sensitive but more rapid growth test. Subsequent to initial tests, using different growth media, a toxicity test procedure was developed which uses a medium with low complexing capacity, a standardized inoculum and a 6 h incubation period.

Two new rapid toxicity tests, based on ingestion activity and digestive enzyme activity of D. magna, were developed and evaluated. The ingestion activity was measured using fluorescent latex micro-beads and an automated microplate fluorimeter allowing a sensitive quantification of the feeding activity of the organisms. The activity of the digestive enzymes, 6-galactosidase, esterase and trypsin, was determined in test organism homogenates using the following fluorogenic{sup 1} and chromogenic{sup 2} substrates: 4-methylumbelliferyl-{beta}-D galactoside{sup 1}, fluorescin diacetate{sup 1} and N-Benzoyl-L-arginine-4-nitroanilide{sup 2}. Both biomarker techniques were developed to allow rapid toxicityscreening on a routine basis. The toxicity of the pore waters of eight contaminated samples was assessed with the aid of the developed biomarker assays. Comparison of the conventional 24h EC50 values with the EC50 values obtained with the 1.5h ingestion test and the threshold concentrations of the 2h digestive enzyme tests revealed a positive correlation between the different effect concentrations. A similar correlation (r{sup 2} = 0.87) between the conventional 24h EC50 values and 1.5h EC50 values was observed in toxicity tests with pure compounds. Correlation coefficients for the relationships between the 3 enzyme effect concentrations and the 24h EC50 values ranged from 0.95 to 0.98, The positive correlations between the conventional and biomarker effect criteria, observed for both environmental samples and pure compounds, demonstrate the potential use of the developed methods as rapid toxicityscreening tools.

To properly maintain a screening machine coal preparation plant operators need to choose the appropriate screening machine for the application and install it properly. The way the feed is distributed to the deck is also important. The screen motion has a big impact on how the machine operates. 1 fig., 4 photos.

Acid volatile sulfides (AVS) have been shown to be an important factor mediating the bioavailability of heavy metals in sediments and have consequently been suggested as a possible predictive tool for toxicity assessment of these matrices. The potential use and limitations of the AVS method for predictive toxicityscreening and priority setting was assessed in a large scale sediment monitoring study (Flanders, Belgium). The acute toxicity of 50 metal contaminated freshwater sediments, with varying metal concentrations and sediment characteristics, were tested using the Microtox{reg_sign} Solid Phase test and the 10 day test with Chironomus riparius and Hyalella azteca. Uni and multivariate statistical techniques were used to asses the relations between acute toxicity and SEM/AVS ratio`s and to evaluate the influence of sediment characteristics on metal bioavailability and toxicity. In general, the results of this study indicate that the AVS-toxicity relationship proposed in literature does have certain limitations. Finally, the potential use of a concentration-addition model for predicting metal-mixture toxicity in sediments will be presented and discussed.

Background: To measure the uptake of first invitation to cervical screening by vaccine status in a population-based cohort offered HPV immunisation in a national catch-up campaign. Methods: A retrospective observational study of routinely collected data from the Scottish Cervical Screening Programme. Data were extracted and linked from the Scottish Cervical Call Recall System, the Scottish Population Register and the Scottish Index of Multiple Deprivation. Records from 201 023 women born between 1 January 1988 and 30 September 1993 were assessed. Women born in or after 1990 were eligible for the national catch-up programme of HPV immunisation. Attendance for screening was within 12 months of the first invitation at age 20 years. Results: There was a significant decline in overall attendance from the 1988 cohort to the 1993 cohort with the adjusted attendance ratio of the 1988 cohort being 1.49 times (95% CI 1.46–1.52) that of the 1993 cohort. Immunisation compensated for this decrease in uptake with unvaccinated individuals having a reduced ratio of attendance compared with those fully vaccinated (RR=0.65, 95% CI 0.64–0.65). Not taking up the opportunity for HPV immunisation was associated with an attendance for screening below the trend line for all women before the availability of HPV immunisation. Conclusions: HPV immunisation is not associated with the reduced attendance for screening that had been feared. Immunised women in the catch-up cohorts appear to be more motivated to attend than unimmunised women, but this may be a result of a greater awareness of health issues. These results, while reassuring, may not be reproduced in routinely immunised women. Continued monitoring of attendance for the first smear and subsequent routine smears is needed. PMID:26794278

Immortalized human lymphoblastoid cell lines have been used to demonstrate that it is possible to use an in vitro model system to identify genetic factors that affect responses to xenobiotics. To extend the application of such studies to investigative toxicology by assessing interindividual and population-wide variability and heritability of chemical-induced toxicity phenotypes, we have used cell lines from the Centre d'Etude du Polymorphisme Humain (CEPH) trios assembled by the HapMap Consortium. Our goal is to aid in the development of predictive in vitro genetics-anchored models of chemical-induced toxicity. Cell lines from the CEPH trios were exposed to three concentrations of 14 environmental chemicals. We assessed ATP production and caspase-3/7 activity 24 h after treatment. Replicate analyses were used to evaluate experimental variability and classify responses. We show that variability of response across the cell lines exists for some, but not all, chemicals, with perfluorooctanoic acid (PFOA) and phenobarbital eliciting the greatest degree of interindividual variability. Although the data for the chemicals used here do not show evidence for broad-sense heritability of toxicity response phenotypes, substantial cell line variation was found, and candidate genetic factors contributing to the variability in response to PFOA were investigated using genome-wide association analysis. The approach of screening chemicals for toxicity in a genetically defined yet diverse in vitro human cell-based system is potentially useful for identification of chemicals that may pose a highest risk, the extent of within-species variability in the population, and genetic loci of interest that potentially contribute to chemical susceptibility.

This review deals with the use of entire plants, seedlings, cell suspension cultures and pollen tubes for the estimation of potential toxicity in the environment, and for risk assessment of chemicals and formulations of human relevance. It is shown that the roots of onions and various crop seedlings, as well as in vitro growing pollen tubes of some mono- and dicotyledonous plants, are most frequently used to obtain toxicity data by determination of root and tube growth inhibition. Both roots and pollen tubes are chloroplast free, non-photosynthetic systems and, therefore, with regard to their cytotoxic reactions are closer to vertebrate tissues and cells than are chloroplast-containing plant organs. Root tips and anthers of flower buds are shown to be applicable to genotoxicity screening by microscopic analysis of mitotic or meiotic aberrations during cell division or microspore development, respectively. The processes of mitosis and meiosis are similar in plants and animals. Therefore, meristematic and sporogenic tissues of plants generally show patterns of cytotoxic response similar to those of embryogenic and spermatogenic tissues of vertebrates. The suitability of root tips, cell suspensions and pollen tubes for the investigation of mechanisms of toxic action and for the analysis of structure-activity relationships is also demonstrated. Two plant-based assays, the Allium test and the pollen tube growth test, both currently being evaluated alongside with established mammalian in vivo and in vitro protocols, are emphasized with regard to their potential use as alternatives to animal in vivo toxicity tests. For both assays, preliminary results indicate that the tips of growing roots and the rapidly elongating pollen tubes of certain higher plant species are as reliable as mammalian cell lines for detecting basal cytotoxicity. It is suggested that seeds and pollen grains, in particular, provide easily storable and convenient systems for inexpensive, relatively

National statistics indicate that 11% of newborns are exposed to drugs of abuse in utero (Chasnoff, Burns, Schnoll, & Burns, 1985). From July through November of 1993, 0.2% (1/583) of infants in our hospital screened positive for exposure to drugs of abuse in utero, by blood and urine screens collected per physician's order. During the same 4 months in 1995, 0.2% (1/574) screened positive. In contrast, from July through November 1994, all newborns born at our institution were screened for in utero drug exposure using meconium samples; approximately 4.5% (22/493) were positive. Meconium screening of all infants, not just those per physician order, produced a dramatic increase in positive drug results. Of great concern in this study was that only two of the 22 mothers identified as having drug-screen positive babies during the 1994 meconium screening agreed to use rehabilitative services. This highlights the necessity of intervention through early educational programs stressing prevention.

Cancer prevention and control efforts serve as national priorities, as cancer is the second leading cause of death in the USA. In addition, cancer disparities exist, with racial/ethnic minority, low-income, and uninsured populations suffering the greatest burden. The goal of this paper is to describe the role that effective health communication can play in increasing routine cancer screening among medically underserved populations, thus decreasing persistent health disparities. For this paper, we applied Sorenson's integrated model of health literacy as a framework for identifying communication gaps and opportunities that can help improve cancer screening specifically at federally qualified health centers (FQHCs). This integrated model consists of four interrelated dimensions: access, understand, appraise, and apply. Employing communication strategies across this health literacy framework has the potential to facilitate improved decision making and cancer screening outcomes among the most underserved populations.

CKD is an important public health problem associated with substantial morbidity, impaired quality of life, shortened life expectancy, and excessive health care costs. Given its long preclinical latency, screening of asymptomatic individuals for CKD has been considered as a potentially useful means of early detection, with a goal of reducing CKD progression and its complications. A recent clinical practice guideline from the American College of Physicians that recommended against screening for CKD in asymptomatic adults without risk factors has reignited debate regarding CKD screening. Despite the lack of randomized controlled trial evidence showing benefits of CKD screening, even among individuals at increased risk for CKD, such as those with diabetes or hypertension or who are of certain high-risk racial or ethnic groups, a thoughtful and selective approach to CKD screening seems to be cost-effective and clinically valuable. CKD screening is recommended by several nephrology professional societies and appropriate in at-risk asymptomatic individuals with the intent of identifying and managing CKD, diagnosing the etiology of CKD, limiting or preventing CKD progression and its associated cardiovascular disease risk, and minimizing risk of AKI, inappropriate drug dosing, and nephrotoxic injury.

Research on health information exposure focuses primarily on deliberate information seeking behavior and its effects on health. By contrast, this study explores the complementary and perhaps more influential role of health information acquired through exposure to routinely used sources, called scanning. We hypothesized that scanning from non-medical sources, both mediated and interpersonal, affects cancer screening and prevention decisions. A nationally representative longitudinal survey of adults 40 to 70 years (N=2,489) was used to analyze the effects of scanning on three cancer screening behaviors (mammography, PSA, colonoscopy) and three prevention behaviors (exercising, eating fruits and vegetables, dieting to lose weight). After adjustment for baseline behaviors and covariates, scanning at baseline predicted one year later weekly exercise days overall, as well as daily fruits and vegetables servings for those already higher on baseline consumption. Also among those reporting timely screening mammogram behavior at baseline, scanning predicted repeat mammography. Scanning was marginally predictive of PSA uptake among those not reporting a PSA at baseline. While there were strong cross-sectional associations, scanning did not predict dieting or colonoscopy uptake in longitudinal analyses. These analyses provide substantial support for a claim that routine exposure to health content from non-medical sources affects specific health behaviors. PMID:24083417

Background Although 900,000 HIV-infected South Africans receive antiretroviral therapy (ART), the majority of South Africans with HIV remain undiagnosed. Methods We use a published simulation model of HIV case detection and treatment to examine three HIV screening scenarios, in addition to current practice: 1) one-time; 2) every five years; and 3) annually. South African model input data include: 16.9% HIV prevalence, 1.3% annual incidence, 49% test acceptance rate, HIV testing costs of $6.49/patient, and a 47% linkage-to-care rate (including two sequential ART regimens) for identified cases. Outcomes include life expectancy, direct medical costs, and incremental cost-effectiveness. Results HIV screening one-time, every five years, and annually increase HIV-infected quality-adjusted life expectancy (mean age 33 years) from 180.6 months (current practice) to 184.9, 187.6 and 197.2 months. The incremental cost-effectiveness of one-time screening is dominated by screening every five years. Screening every five years and annually each have incremental cost-effectiveness ratios of $1,570/quality-adjusted life year (QALY) and $1,720/QALY. Screening annually is very cost-effective even in settings with the lowest incidence/prevalence, with test acceptance and linkage rates both as low as 20%, or when accounting for a stigma impact at least four-fold that of the base case. Conclusions In South Africa, annual voluntary HIV screening offers substantial clinical benefit and is very cost-effective, even with highly constrained access to care and treatment. PMID:21068674

Screening and confirming the presence of drugs and toxic compounds in various matrices are important and challenging tasks routinely faced by forensic and clinical laboratories. Recent advances in the liquid chromatographic and mass spectrometric technologies have provided an opportunity for the development of more specific and effective approaches to achieve the "screening" and "confirmation" goals in a single analytical step. The objectives of this study are: (i) the establishment of an ultra-high performance liquid chromatographic, quadrupole time-of-flight mass spectrometric mass spectrometric and MS-MS spectral database, including 1,200 compounds of interest; and (ii) the development of an effective protocol, using this database and three searching algorithms, for general unknown screening of these compounds. The established database and protocol were evaluated through the analysis of 30 external proficiency test and 100 postmortem samples and found to be significantly more effective than the LC-IT-MS and GC-MS approaches previously established in our laboratory.

A 52-year-old man was found to have a severely dilated aortic root and a Stanford type A dissection on familial screening echocardiography, following diagnosis of a dilated aorta in his son. The dissection required urgent surgical repair. Clinical examination suggested features of Loeys-Dietz syndrome type II, and subsequent demonstration of a mutation in the TGFBR1 gene in the patient and his son confirmed the diagnosis. This article highlights the high prevalence of inherited conditions in dilated aortic root presentations and the importance of family screening and surveillance to allow early surgical intervention. PMID:24495977

As part of the chemical screening and prioritization research program of the U.S. Environmental Protection Agency, the toxicity of the 320 ToxCast™ Phase I chemicals were assessed using a vertebrate screen of developmental toxicity. Zebrafish embryos/larvae (Danio rerio) were exp...

Background Prior to implementing screening programs for acute HIV infection in developing countries, key issues including cost, feasibility, and public health impact must be determined. We compared fourth-generation enzyme immunoassay (EIA) with pooled HIV-1 RNA assays for the detection of acute and early HIV infection in counseling and testing populations in Lima, Peru. Methods Adults presenting for HIV testing at designated clinics in Lima-Callao, Peru were offered additional screening for acute HIV infection. All serum samples were tested with fourth-generation Ag/Ab EIA and confirmed by line immunoassay (LIA). Negative specimens were combined into 50-sample pools for HIV-1 RNA screening by PCR analysis in standard pooling algorithms. RNA-positive samples were re-tested with a third-generation EIA to evaluate the relative sensitivity of standard testing procedures. Results Between 2007 and 2008 we recruited 1,191 participants. The prevalence of HIV infection was 3.2% (38/1191; 2.2-4.2%) overall and 10.6% (25/237; CI=6.6-14.5%) among men who reported sex with men (MSM). The prevalence of acute or recent HIV infection was 0.2% (CI=0-0.4%) overall and 0.8% (CI=0-2.0%) among MSM. Compared with third generation EIA testing, both fourth generation EIA and RNA PCR increased the rate of HIV case identification by 5.6% overall and by 8.0% within the subpopulation of MSM. Conclusions Screening for acute HIV infection within Peru's resource-limited public health system was acceptable and detected a high prevalence of acute and recent HIV infection among MSM. Additional efforts are needed to screen for and prevent transmission of HIV among MSM in Peru during the acute seroconversion stage. PMID:21113069

Background Clinical practice guidelines suggest routinescreening for distress among cancer patients for immediate early psychiatric care. However, previous studies focusing on routinescreening for psychological distress among cancer inpatients in Taiwan are scant. Thus, the aim of this study was to evaluate the prevalence and related factors of psychological distress and mental illness among cancer inpatients in Taiwan. Patients and methods This study was conducted as a retrospective chart review in a general hospital in southern Taiwan. Cancer inpatients were regularly screened by nursing staff using the Distress Thermometer and the 12-item Chinese Health Questionnaire. Positive screening results on either instrument were followed by a non-commanded referral to psychiatrists for clinical psychiatric diagnosis and treatment. Results Of the 810 participants in this study, 179 (22.1%) were recognized as having psychological distress. Younger age (odds ratio [OR] =1.82), having head and neck cancer (OR =2.43), and having not received chemotherapy (OR =1.58) were significantly related to psychological distress. Among the 56 patients (31.3%) with psychological distress who were referred to psychiatrists, the most common mental illness was adjustment disorder (n=22, 39.2%), followed by major depressive disorder (n=13, 23.2%), depressive disorder not otherwise specified (n=6, 10.7%), and anxiety disorder not otherwise specified (n=4, 7.1%). Conclusion Our study indicated that cancer inpatients with psychological distress were more likely to be younger in age, have head and neck cancer, and have not received chemotherapy. The most common psychiatric disorder was adjustment disorder. Early detection of psychological distress and prompt psychiatric consultation and management are very important for cancer inpatients. PMID:27822049

Background The United States health care system remains far from implementing the Centers for Disease Control and Prevention's recommendation of routine human immunodeficiency virus (HIV) screening as part of health care for adults. Although consensus for the importance of screening has grown, innovations in implementing routinescreening are still lacking. HIV on the Frontlines of Communities in the United States (FOCUS) was launched in 2010 to provide an environment for testing innovative approaches to routine HIV screening and linkage to care. Objective The strategy of the FOCUS program was to develop models that maximize the use of information systems, fully integrate HIV screening into clinical practice, transform basic perceptions about routine HIV screening, and capitalize on emerging technologies in health care settings and laboratories. Methods In 10 of the most highly impacted cities, the FOCUS program supports 153 partnerships to increase routine HIV screening in clinical and community settings. Results From program launch in 2010 through October 2013, the partnerships have resulted in a total of 799,573 HIV tests and 0.68% (5425/799,573) tested positive. Conclusions The FOCUS program is a unique model that will identify best practices for HIV screening and linkage to care. PMID:25093431

For all of us working in the field of inherited heart conditions, our ultimate aim is the prevention of sudden cardiac death in young people in our communities. We share the passion and drive to this aim with our colleagues Saul et al, who write to advocate infant screening of infants for LQTS. Although Saul et al aimed to write an unbiased review of the subject, they present data that support screening while underrepresenting evidence against it. Their illustrative Figure 1 is arguably misleading, presenting a graph of freedom from any cardiac event in symptomatic individuals with familial LQTS. We know that 87% of deaths from LQTS occur in those who were previously symptomatic. This discussion, however, is not about symptomatic patients with LQTS; it is about the detection of presymptomatic individuals on a community level. Our aim is to present evidence that has led us to oppose the conclusions and suggestions of their article. Most pediatric cardiologists do not wish to see ECG screening in infancy, and we are among them. Saul et al state that there is sufficient evidence to propose ECG screening in infancy for LQTS. We disagree. We disagree with this view for a number of reasons: (1) The effectiveness of such a program has not been evaluated in terms of outcome. (2) The ECG is an unreliable diagnostic tool with unacceptable reproducibility, specificity, and sensitivity. (3) The adverse effects of overdiagnosing or underdiagnosing LQTS in thousands of individuals have not been evaluated. (4) There are no definitive criterion standard by which LQTS can be excluded once the possibility is raised, and in particular genetic testing is not sensitive or specific enough to do so. (5) There is a paucity of normative ECG and genetic data for non-Whites. We propose what we believe is a more attractive alternative: the detection of LQTS in the community through an active multidisciplinary program to detect probands and screen family members, based around a clinical

Vitamin E can be a prooxidant in isolated lipoprotein suspensions. Because lipid emulsions used in parenteral nutrition are lipoprotein-like suspensions rich in polyunsaturated fatty acids and vitamin E, we hypothesized that vitamin E may act as a prooxidant in lipid emulsions, as it is in lipoprotein suspensions. We therefore exposed an intravenously administered lipid emulsion (Intralipid) to a single spotlight commonly used in the treatment of neonatal jaundice, and measured the formation of triglyceride hydroperoxides by using high-performance liquid chromatography with postcolumn chemiluminescence detection. Concentrations of these hydroperoxides in different batches of fresh intralipid were usually approximately 10 mumol/L but increased up to 60 times after exposure to phototherapy light for a period of 24 hours, even though significant amounts of vitamin E were present at the end of the exposure. Triglyceride hydroperoxides were formed during phototherapy light exposure whether the intralipid was in plastic tubing used routinely for infusion or in glass containers. Ambient light also caused significant peroxidation of the formula lipids, although to a much lesser extent than observed with phototherapy light. For infants in the neonatal intensive care unit who were receiving intralipid but not phototherapy, solutions being infused at the end of 24 hours contained a mean of 40 mumol/L hydroperoxides. For infants receiving phototherapy, the mean was 97 mumol/L. Phototherapy light-induced formation of triglyceride hydroperoxides was prevented by covering the intralipid with aluminum foil or supplementation with sodium ascorbate before light exposure. We conclude that intralipid is highly susceptible to oxidation and that elevated levels of oxidized lipids can be formed during its clinical use, especially when intralipid infusion is combined with phototherapy. Because lipid hydroperoxides are cytotoxic and can cause adverse effects, inadvertent infusion of rancid

Background: Congenital anomalies are among the leading causes of fetal and infant morbidity and mortality worldwide. Prenatal ultrasound (US) screening has become an essential part of antenatal care in the developed world. Such practice is just evolving in the developing countries such as Nigeria. The aim of this article is to present our initial experience and demonstrate the effectiveness of a prenatal US screening program in detecting congenital malformation in a developing country. Materials and Methods: This was a prospective evaluation of the prenatal US screenings conducted at a major referral hospital in Southwestern Nigeria. All pregnant women referred to the antenatal clinic for mid-trimester screening during the period of study were assessed. Results: Two hundred and eighty-seven pregnant women (5 with twin gestations) were presented for fetal anomaly scan during the study period. Twenty-nine anomalies (9.9%) were detected among the scanned population. Sixteen of the anomalies were followed to delivery/termination with a specificity of 93.5%. The commonest malformations were demonstrated in the genitourinary tract (34.5%) followed by malformations within the central nervous system (27.6%). Six (20.6%) of the anomalies were lethal. Five of the anomalies were surgically correctable. Conclusion: Institutions and hospitals across Nigeria and other low- and middle-income countries need to develop policies and programs that would incorporate a standardized routinescreening prenatal US in order to improve feto-maternal well-being and reduce the high perinatal mortality and morbidity in developing nations. PMID:26759511

Aiming to detect individuals of Native American maternal or paternal ancestry a rapid screening approach has been developed. Its strategy was based on SNP typing by Real Time PCR (rt-PCR) followed by High Resolution Melting analysis (HRM). After extraction, DNA was quantitated by rt-PCR using commercial kits; samples were then submitted to two multiplex reactions in order to determine the major Native American mtDNA and Y-chromosome haplogroups by HRM. One cocktail included primers flanking nucleotide substitutions that define mtDNA haplogroup C and sub-haplogroups A2, B2, and D1. The other included primers flanking Y-SNPs M3, M269 and U179 that allowed discriminating Q and non-Q haplogroups. In all cases amplicons were <125 nucleotides long in order to increase the peak resolution. The accuracy of the results obtained was established by means of sequencing analysis of the amplicons. The new working-flow here proposed facilitates and speeds-up the screening process that may preclude a detailed sequencing analysis of particular samples, or for further molecular epidemiological investigations in which continental origin influences might be relevant.

Bacterial contamination of blood components is the principal infectious complication linked to transfusion. The aim of the study was to evaluate the applicability of an automated culture system for platelets. 10 141 platelet concentrates were cultured individually and in pools of five on storage days 1 and 7 using Bact/Alert system aerobic bottles. A modified collection bag was used for improved sampling. Five-millilitre samples were cultured at 37 degrees C for 7 days. Only those samples where the same bacteria were identified in reculture were considered true positives (TP). Homogeneity of proportions was tested by Fisher's exact test. The rate of TP was 30 per 100 000 (95% CI, 6.1-86.4) sampling on day 1; 33 per 100 000 (95% CI, 7-96) on day 7; and 40 per 100 000 (95% CI, 1.28-122.4) if the screening was based on taking both samples (day 1 and 7). Only one TP was detected in the pool testing. The time for detection among TPs on day 1 ranged between 30 and 134 h. The system is not considered practical for use as a routinescreening method, as the time for detection is too long. Pool testing is insensitive. Faster screening methods or pathogen-inactivation systems are needed.

To assess the outcome of routine sexually transmitted infection re-screening after a three-month interval in unselected patients diagnosed with gonorrhoea, we sought to assess whether this active approach would result in an increase in the number of people attending clinic and subsequently diagnosed with gonorrhoea re-infection, compared with normal re-presentation rates. A recall group of patients were invited for re-screening three months after their initial diagnosis of gonorrhoea. Permission was sought to send a reminder two weeks prior to their scheduled recall appointment. Comparisons were made with a historical control group of patients with gonorrhoea in the absence of any formal recall. Of the 242 patients in the intervention arm, 96 (40%) re-attended within six months, and 15 (6%) tested gonorrhoea positive. Two hundred and two patients were assessed in the control group, of whom 45 (22%) re-attended within six months, and 13 (6%) tested gonorrhoea positive. Women were more likely than men to re-attend following active recall, but they were not at higher risk of re-attending while re-infected with gonorrhoea. Active recall following a gonorrhoea diagnosis significantly increases re-attendance rates for repeat screening but did not result in an increased number of subsequent gonorrhoea diagnoses.

A screening programme for fetal abnormalities began at The Hillingdon Hospital in July 1986. Second trimester ultrasound scans are performed by radiographers. A combined prospective and retrospective study of the ultrasound findings and outcome in all pregnancies delivered in 1989-1990 was undertaken. 6412 babies were born during this period, of whom 6183 (96%) were examined by ultrasound in the second trimester; 29 pregnancies were terminated for fetal abnormality. Of the 89 fetuses who were abnormal at birth or at induced termination of the pregnancy (1.4%), 84 were scanned in the second trimester. In 51 cases the abnormality was detected before 22 weeks gestation (sensitivity, 60.7%). 56 of these 84 abnormal fetuses scanned had potentially lethal or major handicapping abnormalities of which 41 were detected by ultrasound before 22 weeks gestation (sensitivity, 73%). There was one false positive diagnosis of abnormality which did not affect outcome. 6352 babies were normal at delivery or on discharge from hospital (specificity, 99.98%).

The preparticipation physical examination (PPE) is a screening tool endorsed by numerous organizations and used to evaluate young athletes prior to competition for both medical and musculoskeletal conditions that may predispose them to injury. The cardiac portion of the examination, as recommended by the American Heart Association, is detailed specifically to detect signs or symptoms consistent with certain congenital heart conditions that may increase a young athlete's risk of sudden cardiac death (SCD). Much controversy has erupted over the years as to whether this examination has the diagnostic sensitivity to detect these conditions and prevent SCD, and whether additional modalities, such as the 12-lead electrocardiograph (ECG), should be incorporated. Given the rarity of SCD events, the large population of young athletes that would qualify yearly for the examination, and the limitations that an ECG would present, it would not be efficient to add the ECG to the standard PPE on the symptomatic athlete. More efforts should be spent in standardizing the PPE on a national level to further improve its efficiency.

Beaches worldwide provide recreational opportunities to hundreds of millions of people and serve as important components of coastal economies. Beach water is often monitored for microbiological quality to detect the presence of indicators of human sewage contamination so as to prevent public health outbreaks associated with water contact. However, growing evidence suggests that beach sand can harbor microbes harmful to human health, often in concentrations greater than the beach water. Currently, there are no standards for monitoring, sampling, analyzing, or managing beach sand quality. In addition to indicator microbes, growing evidence has identified pathogenic bacteria, viruses, and fungi in a variety of beach sands worldwide. The public health threat associated with these populations through direct and indirect contact is unknown because so little research has been conducted relating to health outcomes associated with sand quality. In this manuscript, we present the consensus findings of a workshop of experts convened in Lisbon, Portugal to discuss the current state of knowledge on beach sand microbiological quality and to develop suggestions for standardizing the evaluation of sand at coastal beaches. The expert group at the “Microareias 2012” workshop recommends that 1) beach sand should be screened for a variety of pathogens harmful to human health, and sand monitoring should then be initiated alongside regular water monitoring; 2) sampling and analysis protocols should be standardized to allow proper comparisons among beach locations; and 3) further studies are needed to estimate human health risk with exposure to contaminated beach sand. Much of the manuscript is focused on research specific to Portugal, but similar results have been found elsewhere, and the findings have worldwide implications.

Beaches worldwide provide recreational opportunities to hundreds of millions of people and serve as important components of coastal economies. Beach water is often monitored for microbiological quality to detect the presence of indicators of human sewage contamination so as to prevent public health outbreaks associated with water contact. However, growing evidence suggests that beach sand can harbor microbes harmful to human health, often in concentrations greater than the beach water. Currently, there are no standards for monitoring, sampling, analyzing, or managing beach sand quality. In addition to indicator microbes, growing evidence has identified pathogenic bacteria, viruses, and fungi in a variety of beach sands worldwide. The public health threat associated with these populations through direct and indirect contact is unknown because so little research has been conducted relating to health outcomes associated with sand quality. In this manuscript, we present the consensus findings of a workshop of experts convened in Lisbon, Portugal to discuss the current state of knowledge on beach sand microbiological quality and to develop suggestions for standardizing the evaluation of sand at coastal beaches. The expert group at the "Microareias 2012" workshop recommends that 1) beach sand should be screened for a variety of pathogens harmful to human health, and sand monitoring should then be initiated alongside regular water monitoring; 2) sampling and analysis protocols should be standardized to allow proper comparisons among beach locations; and 3) further studies are needed to estimate human health risk with exposure to contaminated beach sand. Much of the manuscript is focused on research specific to Portugal, but similar results have been found elsewhere, and the findings have worldwide implications.

High-throughput screening (HTS) assays that measure the in vitro toxicity of environmental compounds have been widely applied as an alternative to in vivo animal tests of chemical toxicity. Current HTS studies provide the community with rich toxicology information that has the potential to be integrated into toxicity research. The available in vitro toxicity data is updated daily in structured formats (e.g., deposited into PubChem and other data-sharing web portals) or in an unstructured way (papers, laboratory reports, toxicity Web site updates, etc.). The information derived from the current toxicity data is so large and complex that it becomes difficult to process using available database management tools or traditional data processing applications. For this reason, it is necessary to develop a big data approach when conducting modern chemical toxicity research. In vitro data for a compound, obtained from meaningful bioassays, can be viewed as a response profile that gives detailed information about the compound’s ability to affect relevant biological proteins/receptors. This information is critical for the evaluation of complex bioactivities (e.g., animal toxicities) and grows rapidly as big data in toxicology communities. This review focuses mainly on the existing structured in vitro data (e.g., PubChem data sets) as response profiles for compounds of environmental interest (e.g., potential human/animal toxicants). Potential modeling and mining tools to use the current big data pool in chemical toxicity research are also described. PMID:25195622

High-throughput screening (HTS) assays that measure the in vitro toxicity of environmental compounds have been widely applied as an alternative to in vivo animal tests of chemical toxicity. Current HTS studies provide the community with rich toxicology information that has the potential to be integrated into toxicity research. The available in vitro toxicity data is updated daily in structured formats (e.g., deposited into PubChem and other data-sharing web portals) or in an unstructured way (papers, laboratory reports, toxicity Web site updates, etc.). The information derived from the current toxicity data is so large and complex that it becomes difficult to process using available database management tools or traditional data processing applications. For this reason, it is necessary to develop a big data approach when conducting modern chemical toxicity research. In vitro data for a compound, obtained from meaningful bioassays, can be viewed as a response profile that gives detailed information about the compound's ability to affect relevant biological proteins/receptors. This information is critical for the evaluation of complex bioactivities (e.g., animal toxicities) and grows rapidly as big data in toxicology communities. This review focuses mainly on the existing structured in vitro data (e.g., PubChem data sets) as response profiles for compounds of environmental interest (e.g., potential human/animal toxicants). Potential modeling and mining tools to use the current big data pool in chemical toxicity research are also described.

High-throughput in vitro toxicityscreening can provide an efficient way to identify potential biological targets for chemicals. However, relying on nominal assay concentrations may misrepresent potential in vivo effects of these chemicals due to differences in bioavailability, c...

Introduction Vitamin B12 deficiency is mainly diagnosed in symptomatic patients. However, the deficiency may also be prevalent in asymptomatic patients. Our aim was to study the prevalence of Vit B12 deficiency in IT professionals (Information Technology Professionals from Software industry) who presented for routine health screening and to correlate the deficiency to various parameters. Materials and Methods This was single centre, observational study comprising of 84 IT professionals. The data was collected in structured format. The study was designed to identify prevalence of Vit B12 deficiency and correlate to other factors such as type of diet, income level & regular use of medication (such as Antacid & Metformin). Results Total 28 individuals were found to be deficient (33.34%). Prevalence of Vit B12 deficiency amongst Vegetarian and non vegetarian diet adhering subjects was 47.5% and 20.45% respectively. B12 deficiency was also prevalent in high income age group. Further chronic intake of PPI (Proton pump inhibitor) and Metformin was associated with prevalence of 37.5% and 33.34% in the present study. Conclusion During health screening of IT Professionals, significant prevalence of Vit B12 deficiency was noted across all income groups & non vegetarian diet consuming subjects also. There is significant correlation between Vit B12 deficiency with chronic use of PPI and Metformin. PMID:26816929

Recent efforts directed at potential litigation in Hawai‘i have resulted in a renewed interest for genetic screening for cytochrome P450 2C19 (CYP2C19) polymorphisms in patients treated with clopidogrel. Clopidogrel is an antiplatelet agent, frequently used in combination with aspirin, for the prevention of thrombotic complications with acute coronary syndrome and in patients undergoing percutaneous coronary interventions. Cytochrome P-450 (CYP) 2C19 is an enzyme involved in the bioactivation of clopidogrel from a pro-drug to an active inhibitor of platelet action. Patients of Asian and Pacific Island background have been reported to have an increase in CYP2C19 polymorphisms associated with loss-of-function of this enzyme when compared to other ethnicities. This has created an interest in genetic testing for CYP2C19 polymorphisms in Hawai‘i. Based upon our review of the current literature, we do not feel that there is support for the routinescreening for CYP2C19 polymorphisms in patients being treated with clopidogrel; furthermore, the results of genetic testing may not be helpful in guiding therapeutic decisions. We recommend that decisions on the type of antiplatelet treatment be made based upon clinical evidence of potential differential outcomes associated with the use of these agents rather than on the basis of genetic testing. PMID:25628978

Screening whole effluent toxicity tests are cost/effective methods for detecting the presence of toxic concentrations of unknown pollutants, but the application must solve the problem associated with the effect of high and variable concentrations of nutrients in the effluent on the results of algal toxicity tests. This work proposes a cost/effective test, based on three dilution levels measured at a single point time and a discriminant model for establishing if this kind of complex samples, with difficult interpretation of dilution-response curves, should be considered toxic to algae. This procedure identified properly around 85% of the samples considered toxic by expert judgement.

The workbook provides a logical approach to the selection of appropriate screening techniques for estimating ambient concentrations due to various toxic/hazardous pollutant releases. Methods used in the workbook apply to situations where a release can be fairly well-defined, a condition typically associated with non-accidental toxic releases. The format of the workbook is built around a series of release scenarios which may be considered typical and representative of the means by which toxic chemicals become airborne.

The ToxCast program was developed by the U.S. EPA's National Center for Computational Toxicology to provide cost-effective high-throughput screening for the potential toxicity of thousands of chemicals. Phase I screened 309 compounds in over 500 assays to evaluate concentration-...

Objectives To evaluate the evidence relating to the effectiveness of breast self-examination (BSE) to screen for breast cancer and to provide recommendations for routine teaching of BSE to women in various age groups as part of a periodic health examination. Options Routine teaching of BSE to women. Evidence The electronic databases MEDLINE, PreMEDLINE, CINAHL, HealthSTAR, Current Contents and the Cochrane Library were searched for abstracts and full reports of studies published from 1966 to October 2000 that evaluated the effectiveness of BSE in reducing breast cancer mortality. In addition, references of key papers were searched and experts consulted to ensure that all relevant articles had been identified. Outcomes Prevention of death from breast cancer was viewed as the most important outcome; other outcomes examined included the stage of cancer detected, the rate of benign biopsy results, the number of patient visits for breast complaints, and psychological benefits and harms. Values The recommendations of this report reflect the commitment of the Canadian Task Force on Preventive Health Care to provide a structured, evidence-based appraisal of whether a manoeuvre should be included in the periodic health examination. Benefits, harms and costs Breast cancer is the most frequently diagnosed cancer among Canadian women, accounting for 30% of all new cancer cases each year. In 2000 an estimated 19 200 Canadian women would have been diagnosed with breast cancer, and 5500 would have died from the disease. To date, 2 large randomized controlled trials, a quasi-randomized trial, a large cohort study and several case–control studies have failed to show a benefit for regular performance of BSE or BSE education, compared with no BSE. In contrast, there is good evidence of harm from BSE instruction, including significant increases in the number of physician visits for the evaluation of benign breast lesions and significantly higher rates of benign biopsy results

A lack of affordable and effective testing and screening procedures mean surprisingly little is known about the health hazards of many of the tens of thousands of chemicals in use in the world today. The recent rise in the number of children affected by neurological disorders such as autism has stirred valuable debate about the role chemicals play in our daily life, highlighting the need for improved methods of assessing chemicals for developmental neural toxicity. Current methods of testing chemicals for developmental neural toxicity include animal testing with rats or mice and in vitro testing using cultured primary cells or cell lines. Here, we review the current state of neural toxicityscreening, analyze the limitations of these methods and, under the National Institutes of Health's new Microphysiological Systems initiative, describe a human pluripotent stem cell-based platform for developmental neural toxicityscreens. PMID:24565336

The present report highlights the possible adverse effects of doxylamine, a common over the counter sleep aid. Doxylamine is an antihistamine that at toxic doses can cause anticholinergic effects, including seizures, rhabdomyolysis and death. The following case describes a patient with doxylamine toxicity who presented with seizure and confusion. Our patient was managed symptomatically, and remained otherwise stable throughout his hospitalisation. This case is atypical in terms of a delayed rhabdomyolysis and a false positive urine drug screen test for methadone. There is evidence that doxylamine at toxic levels can lead to false positives for methadone and phencyclidine testing using immunoassay-based urine drug screen kits. Urine drug screen testing on patients who are hospitalised is typically performed using immunoassays. However, in certain cases confirmatory secondary testing may be required. Doxylamine is prone to abuse and knowledge of the clinical presentation of its toxicity and the management of acute overdose can be life-saving.

Validation of alternative assays requires comparison of the responses to toxicants in the alternative assay with in vivo responses. Chemicals have been classified as "positive" or "negative" in vivo, despite the fact that developmental toxicity is conditional on magnitude of exposure. We developed a list of positive and negative developmental exposures, with exposure defined by toxicokinetic data, specifically maternal plasma Cmax . We selected a series of 20 chemicals that caused developmental toxicity and for which there were appropriate toxicokinetic data. Where possible, we used the same chemical for both positive and negative exposures, the positive being the Cmax at a dose level that produced significant teratogenicity or embryolethality, the negative being the Cmax at a dose level not causing developmental toxicity. It was not possible to find toxicokinetic data at the no-effect level for all positive compounds, and the negative exposure list contains Cmax values for some compounds that do not have developmental toxicity up to the highest dose level tested. This exposure-based reference list represents a fundamentally different approach to the evaluation of alternative tests and is proposed as a step toward application of alternative tests in quantitative risk assessment.

Bioassay results from two field studies illustrate how maps of toxicity can be prepared based on systematic sampling and show how cleanup decisions can be made using bioassay results based on few samples. Logarithmically spaced soil samples were obtained along four parallel transects at the Rocky Mountain Arsenal. A total of 72 soil samples were subjected to Daphnia, Microtox, algal, earthworm and lettuce root elongation bioassays. Bioassay results (excepting earthworms) were inconclusive for toxicity, but allowed us to ignore several classes of compounds, such as water-soluble heavy metals, herbicides, and insecticides, since our prior results using pure chemicals showed depressed algal growth in the presence of these contaminants. To depict the spatial pattern of observed seed mortality at each depth, we used kriging to produce contour maps. The results clearly showed that lettuce seed mortality was higher in the 15 to 30 cm fraction, that waste-trench soil was highly phytotoxic, and that toxicity decreased as a function of distance from the trench. In addition, we found that mortality contours produced by kriging could be useful in site cleanup decisions. A study was conducted using a series of water and sediment samples collected from a narrow stream adjacent to a wood treatment plant in Canton, Mississippi. Both creosote and pentachlorophenol were used for wood treatment. Sediment samples were collected every 20 m in the visibly contaminated zones. Based on simple linear interpolation of bioassay results, we found that different bioassays led to different conclusions regarding the toxicity of different areas, suggesting that contaminants other than creosote may have caused the observed toxicity. Moreover, chemical analysis was an inaccurate predictor of toxicity.

AbstractCigarette smoking is unrivaled among developmental toxicants in terms of total adverse impact on the human population. According to the American Lung Association, smoking during pregnancy is estimated to account for 20 to 30 percent of low-weight babies, up to 14 per...

BACKGROUND: There continues to be many efforts around the world to develop assays that are shorter than the traditional embryofetal developmental toxicity assay, or use fewer or no mammals, or use less compound, or have all three attributes. Each assay developer needs to test th...

Because drug-induced liver injury is one of the main reasons for drug development failures, it is important to perform drug toxicityscreening in the early phase of pharmaceutical development. Currently, primary human hepatocytes are most widely used for the prediction of drug-induced liver injury. However, the sources of primary human hepatocytes are limited, making it difficult to supply the abundant quantities required for large-scale drug toxicityscreening. Therefore, there is an urgent need for a novel unlimited, efficient, inexpensive, and predictive model which can be applied for large-scale drug toxicityscreening. Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are able to replicate indefinitely and differentiate into most of the body's cell types, including hepatocytes. It is expected that hepatocyte-like cells generated from human ES/iPS cells (human ES/iPS-HLCs) will be a useful tool for drug toxicityscreening. To apply human ES/iPS-HLCs to various applications including drug toxicityscreening, homogenous and functional HLCs must be differentiated from human ES/iPS cells. In this review, we will introduce the current status of hepatocyte differentiation technology from human ES/iPS cells and a novel method to predict drug-induced liver injury using human ES/iPS-HLCs.

A time-integrated sampling device interfaced with two toxicity-based assays is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethylsulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor...

Proteus mirabilis is a common urinary tract pathogen, and may induce various inflammation symptoms. Its notorious ability to resist multiple antibiotics and to form urinary tract stones makes its treatment a long and painful process, which is further challenged by the frequent horizontal gene transferring events in P. mirabilis genomes. Three strains of P. mirabilis C02011/C04010/C04013 were isolated from a local outbreak of a food poisoning event in Shenzhen, China. Our hypothesis is that new genes may have been acquired horizontally to exert the digestion tract infection and toxicity. The functional characterization of these three genomes shows that each of them independently acquired dozens of virulent genes horizontally from the other microbial genomes. The representative strain C02011 induces the symptoms of both vomit and diarrhea, and has recently acquired a complete type IV secretion system and digestion tract toxic genes from the other bacteria.

A promising new and rapid toxicityscreening test was developed, the concept and principles of which are presented. The method consists of visual observation of in vivo inhibition of an enzymatic process, using a fluorescent substrate. Juvenile Daphnia magna was exposed to a toxicant dilution series for 1 h, after which the substrate was added and the enzymatic inhibition was observed visually, using a long-wave UV light. The 1-h EC50 results of 11 pure compounds are presented and compared to the conventional 24- and 48-h Daphnia magna EC50s. All 1-h fluorescence EC50s were of the same order of magnitude and correlated very well with the 24- and 48-h EC50s. The sensitivity and reproducibility of this cost-effective screening test were compared to those of the Microtox[reg sign] test. The scope for application and the potential of this new rapid toxicityscreening test are evaluated.

Between 60% and 80% of all marine litter is plastic. Leachate from plastics has previously been shown to cause acute toxicity in the freshwater species Daphnia magna. Here, we present an initial screening of the marine environmental hazard properties of leachates from weathering plastics to the marine harpacticoid copepod [Crustacea] Nitocra spinipes. Twenty-one plastic products made of different polymeric materials were leached and irradiated with artificial sunlight. Eight of the twenty-one plastics (38%) produced leachates that caused acute toxicity. Differences in toxicity were seen for different plastic products, and depending on the duration of irradiation. There was no consistent trend in how toxicity of leachate from plastics changed as a function of irradiation time. Leachate from four plastics became significantly more toxic after irradiation, two became significantly less toxic and two did not change significantly. Analysis of leachates from polyvinyl chloride (PVC) by liquid chromatography coupled to a full-scan high-resolution mass spectrometer showed that the leachates were a mixture of substances, but did not show evidence of degradation of the polymer backbone. This screening study demonstrates that leachates from different plastics differ in toxicity to N. spinipes and that the toxicity varies under simulated weathering.

Hydroxychloroquine sulfate (HCQ, Plaquenil) is an analogue of chloroquine (CQ), an antimalarial agent, used for the treatment of systemic lupus erythematosus, rheumatoid arthritis and other autoimmune disorders. Its use has been associated with severe retinal toxicity, requiring a discontinuation of therapy. Because it presents potential secondary effects including irreversible maculopathy, knowledge of incidence, risk factors, drug toxicity and protocol screening of the patients it represents important data for the ophthalmologists. Thus, it is imperative that rheumatologists, medical internists and ophthalmologists are aware of the toxicity from hydroxychloroquine they should also be careful to minimize its occurrence and effects.

The protective antigen (PA) of Bacillus anthracis is integral to the mechanism of anthrax poisoning. The cloning, expression and purification of a 32 kDa B. anthracis PA fragment (PA32) is described. This fragment has also been expressed as a fusion construct to stabilized green fluorescent protein (EGFP-PA32). Both proteins were capable of binding to specific cell surface receptors as determined by fluorescent microscopy and a flow cytometric assay. To confirm binding specificity in the flow cytometric assay, non-fluorescent PA83 or PA32 was used to competitively inhibit fluorescent EGFP-PA32 binding to cell receptors. This assay can be employed as a rapid screen for compounds which disrupts binding of PA to cells. Additionally, the high intracellular expression levels and ease of purification make this recombinant protein an attractive vaccine candidate or therapeutic treatment for anthrax poisoning.

Environment and organisms are persistently exposed by a mixture of various substances. However, the current evaluation method is mostly based on an individual substance's toxicity. A systematic toxicity evaluation of heterogeneous substances needs to be established. To demonstrate toxicity assessment of mixture, we chose a group of three typical ingredients in cosmetic sunscreen products that frequently enters ecosystems: benzophenone-3 (BP-3), ethylhexyl methoxycinnamate (EHMC), and titanium dioxide nanoparticle (TiO2 NP). We first determined a range of nominal toxic concentration of each ingredient or substance using Daphnia magna, and then for the subsequent organismal level phenotypic assessment, chose the wild-type zebrafish embryos. Any phenotype change, such as body deformation, led to further examinations on the specific organs of transgenic zebrafish embryos. Based on the systematic toxicity assessments of the heterogeneous substances, we offer a sequential environmental toxicity assessment protocol that starts off by utilizing Daphnia magna to determine a nominal concentration range of each substance and finishes by utilizing the zebrafish embryos to detect defects on the embryos caused by the heterogeneous substances. The protocol showed additive toxic effects of the mixtures. We propose a sequential environmental toxicity assessment protocol for the systematic toxicityscreening of heterogeneous substances from Daphnia magna to zebrafish embryo in-vivo models.

The purpose of this research was to develop a test system for screeningtoxic substances by predicting their aquatic ecosystem effects. The system studied was a static, one liter microcosm with a diverse species assemblage. The microcosm was composed of biotic inoculum, chemically defined medium and sediment. The biotic inoculum contained primary producers, grazers, carnivores and decomposers. Three different types of sediment were studied: sand, clay, and clay plus sand. Four organic chemicals: phenol, triethylene glycol (TEG), quinoline and naphthoquinone were evaluated with this test system. The toxicities of TEG, quinoline and naphthoquinone were compared for each sediment type. Toxicity was evaluated in terms of the chemical's effects on primary productivity and heterotrophic activity though other effects are also noted. Naphthoquinone concentration exhibited no correlation between ecosystem property values and therefore, could not be ranked. Phenol exhibited the greatest toxicity to net production immediately after the toxicant addition. Quinoline was most toxic to net production over the longer time scale. TEG exhibited the least toxicity to net production, however, TEG exhibited higher toxicity to heterotrophic activity than either quinoline or phenol. Although the type of sediment used in the microcosms did not change the relative toxicities of the chemicals, the microcosms with clay sediment always were observed to exhibit lower net production and higher variability.

The EPA ToxCast research program uses high throughput screening for bioactivity profiling and predicting the toxicity of large numbers of chemicals. ToxCast Phase‐I tested 309 well‐characterized chemicals in over 500 assays for a wide range of molecular targets and cellular respo...

Reliable, high throughput, in vitro preliminary screening batteries have the potential to greatly accelerate the rate at which regulatory neurotoxicity data is generated. This study evaluated the importance of astrocytes when predicting acute toxic potential using a neuronal screening battery of pure neuronal (NT2.N) and astrocytic (NT2.A) and integrated neuronal/astrocytic (NT2.N/A) cell systems derived from the human NT2.D1 cell line, using biochemical endpoints (mitochondrial membrane potential (MMP) depolarisation and ATP and GSH depletion). Following exposure for 72 h, the known acute human neurotoxicants trimethyltin-chloride, chloroquine and 6-hydroxydopamine were frequently capable of disrupting biochemical processes in all of the cell systems at non-cytotoxic concentrations. Astrocytes provide key metabolic and protective support to neurons during toxic challenge in vivo and generally the astrocyte containing cell systems showed increased tolerance to toxicant insult compared with the NT2.N mono-culture in vitro. Whilst there was no consistent relationship between MMP, ATP and GSH log IC(50) values for the NT2.N/A and NT2.A cell systems, these data did provide preliminary evidence of modulation of the acute neuronal toxic response by astrocytes. In conclusion, the suitability of NT2 neurons and astrocytes as cell systems for acute toxicityscreening deserves further investigation.

The caatinga, an exclusively Brazilian biome, is one of the most endangered vegetation systems in the planet. To be exploited rationally, its potential needs to be scientifically demonstrated. Among these is the faveleira, used in northeastern Brazil. It stands out for its extraordinary drought resistance and medicinal properties. The objective of this study was to assess the therapeutic potential of compounds extracted from Cnidoscolus quercifolius Pohl in preventing disease and its rational use as a herbal therapeutic tool. The methodology began with the collection and herborization of the plant material, to obtain the chemical compounds, preliminary phytochemical analysis, and extraction of the constituents of the active extracts. To determine the biological activities the authors conducted investigation of antioxidant and antimicrobial activities, inhibition capacity of the acetylcholinesterase enzyme, and initial assessment of toxicity of the extracts. The results demonstrated great potential as an antimicrobial agent, an important antioxidant capacity, and acetylcholinesterase inhibition response with no significant difference compared with the reference drug. The authors expect to develop a new herbal product, resulting in lower production costs and that, consequently, could be commercialized in more accessible form to the population, highlighting the risk reduction of contraindication of this category of medications. PMID:27293464

The caatinga, an exclusively Brazilian biome, is one of the most endangered vegetation systems in the planet. To be exploited rationally, its potential needs to be scientifically demonstrated. Among these is the faveleira, used in northeastern Brazil. It stands out for its extraordinary drought resistance and medicinal properties. The objective of this study was to assess the therapeutic potential of compounds extracted from Cnidoscolus quercifolius Pohl in preventing disease and its rational use as a herbal therapeutic tool. The methodology began with the collection and herborization of the plant material, to obtain the chemical compounds, preliminary phytochemical analysis, and extraction of the constituents of the active extracts. To determine the biological activities the authors conducted investigation of antioxidant and antimicrobial activities, inhibition capacity of the acetylcholinesterase enzyme, and initial assessment of toxicity of the extracts. The results demonstrated great potential as an antimicrobial agent, an important antioxidant capacity, and acetylcholinesterase inhibition response with no significant difference compared with the reference drug. The authors expect to develop a new herbal product, resulting in lower production costs and that, consequently, could be commercialized in more accessible form to the population, highlighting the risk reduction of contraindication of this category of medications.

The U.S. Environmental Protection Agency (EPA), through its ToxCast program, is developing predictive toxicity approaches that will use in vitro high-throughput screening (HTS), high-content screening (HCS) and toxicogenomic data to predict in vivo toxicity phenotypes. There are ...

There is a compelling need to develop information for the screening and prioritization of the health and environmental effects of large numbers of man-made chemicals. Knowledge of the potential pathways for activity provides a rational basis for the preliminary evaluation of ris...

Objectives Postpartum depression (PPD) affects approximately 10-20% of all mothers after giving birth. Adequate screening and follow-up care for the postpartum mother with depression is an essential component of quality care in this population. The purpose of this quality improvement project was to evaluate the quality and quantity of a postnatal PPD screening program and the subsequent initiation of needed PPD treatment in an integrated health system. Methods After implementing a standardized PPD screening process, we conducted an 18-month retrospective study of patient visits that required a PPD screen. Data were abstracted from medical records and analyzed to determine if postnatal PPD screening occurred, what quality of the screening was, and what follow-up measures were taken. Results Within the study timeframe, 28,389 postpartum and well-child visits were eligible for PPD screening. PPD screening occurred at 88% of eligible visits for approximately 5000 unique women. PPD was identified in 8.1% of screened women. Conclusions Of women with PPD, at least 44.8% were prescribed an SSRI and 21.4% attended a visit with a mental health professional, which is consistent with other studies. Screening can be successful through collaboration, although ongoing evaluation and process modification are necessary.

Background Laboratory tests for routine drug of abuse and toxicology (DOA/Tox) screening, often used in emergency medicine, generally utilize antibody-based tests (immunoassays) to detect classes of drugs such as amphetamines, barbiturates, benzodiazepines, opiates, and tricyclic antidepressants, or individual drugs such as cocaine, methadone, and phencyclidine. A key factor in assay sensitivity and specificity is the drugs or drug metabolites that were used as antigenic targets to generate the assay antibodies. All DOA/Tox screening immunoassays can be limited by false positives caused by cross-reactivity from structurally related compounds. For immunoassays targeted at a particular class of drugs, there can also be false negatives if there is failure to detect some drugs or their metabolites within that class. Methods Molecular similarity analysis, a computational method commonly used in drug discovery, was used to calculate structural similarity of a wide range of clinically relevant compounds (prescription and over-the-counter medications, illicit drugs, and clinically significant metabolites) to the target ('antigenic') molecules of DOA/Tox screening tests. These results were compared with cross-reactivity data in the package inserts of immunoassays marketed for clinical testing. The causes for false positives for phencyclidine and tricyclic antidepressant screening immunoassays were investigated at the authors' medical center using gas chromatography/mass spectrometry as a confirmatory method. Results The results illustrate three major challenges for routine DOA/Tox screening immunoassays used in emergency medicine. First, for some classes of drugs, the structural diversity of common drugs within each class has been increasing, thereby making it difficult for a single assay to detect all compounds without compromising specificity. Second, for some screening assays, common 'out-of-class' drugs may be structurally similar to the target compound so that they

Results are reported of a screening programme for galactosaemia covering a period of 2½ years and 6415 births. The gene frequency for galactosaemia estimated from the data of the screening programme was 0·002. This conflicted with the known live-birth incidence of at least 1: 50,000 during this same period. 2 of the 4 galactosaemic infants concerned died under circumstances that were preventable had they been screened at birth. The need to screen all sick infants for galactosaemia is emphasized, as is the requirement for reliable information on its incidence in Great Britain. The screening test employed (Beutler and Baluda, 1966a) seemed appropriate for this purpose. It was simple to perform and apparently accurate in galactosaemic infants. Its accuracy in detecting heterozygotes is uncertain. This test should be available in all hospitals receiving sick neonates. PMID:4401641

The US Centers for Disease Control and Prevention (CDC) recommend human immunodeficiency virus (HIV) screening for all persons aged 13 to 64 years who present to a health care provider. We sought to improve adherence to the CDC guidelines on the Internal Medicine Resident Hospital Service. We surveyed residents about the CDC guidelines, sent email reminders, provided education, and engaged them in friendly competition. Credit for guideline adherence was awarded if an offer of HIV screening was documented at admission, if a screening test was performed, or if a notation in the resident sign out sheet indicated why screening was not performed. We examined HIV screening of a postintervention group of patients admitted between August 8, 2012, and June 30, 2013, and compared them to a preintervention group admitted between August 1, 2011, and June 30, 2012. Postintervention offers of HIV screening increased significantly (7.9% [44/559] vs 55.5% [300/541]; Pscreening (8.9% [50/559] vs 67.5% [365/541]; Pscreening tests was ordered postintervention (7.7% [43/559] vs 44.4% [240/541]; Pscreening documentation ranged from 0% (0/53) to 17% (9/53) preintervention, whereas it ranged from 30.6% (11/36) to 100% (62/62) postintervention. HIV screening adherence can be improved through resident education, friendly competition, and system reminders. Barriers to achieving sustained adherence to the CDC guidelines include a heterogeneous patient population and provider discomfort with the subject. PMID:27239302

A shift in toxicity testing from in vivo to in vitro may efficiently prioritize compounds, reveal new mechanisms, and enable predictive modeling. Quantitative high-throughput screening (qHTS) is a major source of data for computational toxicology, and our goal in this study was to aid in the development of predictive in vitro models of chemical-induced toxicity, anchored on interindividual genetic variability. Eighty-one human lymphoblast cell lines from 27 Centre d'Etude du Polymorphisme Humain trios were exposed to 240 chemical substances (12 concentrations, 0.26nM-46.0μM) and evaluated for cytotoxicity and apoptosis. qHTS screening in the genetically defined population produced robust and reproducible results, which allowed for cross-compound, cross-assay, and cross-individual comparisons. Some compounds were cytotoxic to all cell types at similar concentrations, whereas others exhibited interindividual differences in cytotoxicity. Specifically, the qHTS in a population-based human in vitro model system has several unique aspects that are of utility for toxicity testing, chemical prioritization, and high-throughput risk assessment. First, standardized and high-quality concentration-response profiling, with reproducibility confirmed by comparison with previous experiments, enables prioritization of chemicals for variability in interindividual range in cytotoxicity. Second, genome-wide association analysis of cytotoxicity phenotypes allows exploration of the potential genetic determinants of interindividual variability in toxicity. Furthermore, highly significant associations identified through the analysis of population-level correlations between basal gene expression variability and chemical-induced toxicity suggest plausible mode of action hypotheses for follow-up analyses. We conclude that as the improved resolution of genetic profiling can now be matched with high-quality in vitro screening data, the evaluation of the toxicity pathways and the effects of

compared to existing methods such as ICP-MS. It concludes with a discussion of a number of different FDA applications and case studies in which XRF has been used to screen, identify, and in some cases quantify toxic elements in various products. This work clearly demonstrates that XRF analyzers are an exceedingly valuable tool for routine and nonroutine elemental analysis investigations, both in the laboratory and in the field. In the future, it is hoped that both field-portable and laboratory-grade XRF analyzers will see more widespread use for investigational and forensic-type applications of food and other regulated consumer products.

This study evaluated the use of Nothobranchius guentheri as a novel organism for rapid acute toxicityscreening. A major advantage of the species is that there is no need to maintain a continuous culture to have organisms immediately available for testing. Rather, the embryos are viable under long-term storage conditions and can be hatched within a few hours. The tests require only 24 h with standard laboratory equipment. Sensitivity levels for 11 representative toxicants were comparable to those reported for five of the standard US Environmental Protection Agency test species requiring continuous culture.

Samples of building materials visibly contaminated with moisture-related fungi (drywall, fiberglass, wallpaper, wood) were tested with indirect (FFL) and direct (MTT) cytotoxicity screening tests that are particularly sensitive toStachybotrys chartarum toxins. In addition, microscopic, chemical, immunochemical (Roridin A enzyme immunoassay) and mycological culture analyses were performed. In all cases in which building occupants had reported verifiable skin, mucous membrane, respiratory, central nervous system or neuropsychological abnormalities, cytotoxicity was identified. Results of a cytotoxicity screening test of field samples, such as the direct MTT test method, will give investigators of health problems related to indoor air quality problems important toxicity information.

Background Cryptococcal meningitis is common and associated with high mortality among HIV infected persons. The World Health Organization recommends that routine Cryptococcal antigen (CrAg) screening in ART-naïve adults with a CD4+ count <100 cells/μL followed by pre-emptive antifungal therapy for CrAg-positive patients be considered where CrAg prevalence is ≥3%. The prevalence of CrAg among HIV adults in Namibia is unknown. We estimated CrAg prevalence among HIV-infected adults receiving care in Namibia for the purpose of informing routinescreening strategies. Methods The study design was cross-sectional. De-identified plasma specimens collected for routine CD4+ testing from HIV-infected adults enrolled in HIV care at 181 public health facilities from November 2013 to January 2014 were identified at the national reference laboratory. Remnant plasma from specimens with CD4+ counts <200 cells/μL were sampled and tested for CrAg using the IMMY® Lateral Flow Assay. CrAg prevalence was estimated and assessed for associations with age, sex, and CD4+ count. Results A total of 825 specimens were tested for CrAg. The median (IQR) age of patients from whom specimens were collected was 38 (32–46) years, 45.9% were female and 62.9% of the specimens had CD4 <100 cells/μL. CrAg prevalence was 3.3% overall and 3.9% and 2.3% among samples with CD4+ counts of CD4+<100 cells/μL and 100–200 cells/μL, respectively. CrAg positivity was significantly higher among patients with CD4+ cells/μL < 50 (7.2%, P = 0.001) relative to those with CD4 cells/μL 50–200 (2.2%). Conclusion This is the first study to estimate CrAg prevalence among HIV-infected patients in Namibia. CrAg prevalence of ≥3.0% among patients with CD4+<100 cells/μL justifies routine CrAg screening and preemptive treatment among HIV-infected in Namibia in line with WHO recommendations. Patients with CD4+<100 cells/μL have a significantly greater risk for CrAg positivity. Revised guidelines for ART in

Rapid and routine detection of deoxynivalenol (DON) in cereals-based food and feed has long been a strong desire of regulators and manufacturers. Traditional chemical methods and antibody based biosensors and immunoassays have been developed as viable tools to identify and measure DON. However, thes...

Survey of 58 physicians revealed that they did not routinely ask their pregnant patients about alcohol consumption for several reasons: physician bias resulting from own abuse, lack of training, poor awareness of problem and effects, denial that Fetal Alcohol Syndrome occurs in private practice, time limitations, disinterest, fear of offending…

Statistical examination of animal response data obtained using Procedure B of the USF toxicityscreening test method indicates that the data deviate only slightly from a normal or Gaussian distribution. This slight departure from normality is not expected to invalidate conclusions based on theoretical statistics. Comparison of times to staggering, convulsions, collapse, and death as endpoints shows that time to death appears to be the most reliable endpoint because it offers the lowest probability of missed observations and premature judgements.

Autosomal-dominant polycystic kidney disease (ADPKD) is a systemic disease, marked by progressive increase of bilateral renal cysts, resulting in chronic kidney disease (CKD) and often leading to end-stage renal disease (ESRD). Apart from renal cysts, patients often have extra-renal disease, involving the liver, heart and vasculature. Other less common but equally important extra-renal manifestations of ADPKD include diverticular disease, hernias, male infertility and pain. Extra-renal disease burden is often asymptomatic, but may result in increased morbidity and mortality. If the disease burden is significant, screening may prove beneficial. We review the rationale for current screening recommendations and propose some guidelines for screening and management of ADPKD patients.

The ChemScreen project aimed to develop a screening system for reproductive toxicity based on alternative methods. QSARs can, if adequate, contribute to the evaluation of chemical substances under REACH and may in some cases be applied instead of experimental testing to fill data gaps for information requirements. As no testing for reproductive effects should be performed in REACH on known genotoxic carcinogens or germ cell mutagens with appropriate risk management measures implemented, a QSAR pre-screen for 70,983 REACH substances was performed. Sixteen models and three decision algorithms were used to reach overall predictions of substances with potential effects with the following result: 6.5% genotoxic carcinogens, 16.3% mutagens, 11.5% developmental toxicants. These results are similar to findings in earlier QSAR and experimental studies of chemical inventories, and illustrate how QSAR predictions may be used to identify potential genotoxic carcinogens, mutagens and developmental toxicants by high-throughput virtual screening.

We report herein two cases where detection of X chromosome aneuploidy (cytogenetically proved 45,X/46XX and 47,XXX) was made possible by molecular diagnosis during population-based carrier screening for Fragile X syndrome, using Southern blot analysis. This study emphasizes the value of molecular analysis for gene dosage to suggest chromosomal aneuploidy.

Unexpected toxicity in areas such as cardiotoxicity, hepatotoxicity, and neurotoxicity is a serious complication of clinical therapy and one of the key causes for failure of promising drug candidates in development. Animal studies have been widely used for toxicology research to provide preclinical security evaluation of various therapeutic agents under development. Species differences in drug penetration of the blood-brain barrier, drug metabolism, and related toxicity contribute to failure of drug trials from animal models to human. The existing system for drug discovery has relied on immortalized cell lines, animal models of human disease, and clinical trials in humans. Moreover, drug candidates that are passed as being safe in the preclinical stage often show toxic effects during the clinical stage. Only around 16% drugs are approved for human use. Research on induced pluripotent stem cells (iPSCs) promises to enhance drug discovery and development by providing simple, reproducible, and economically effective tools for drug toxicityscreening under development and, on the other hand, for studying the disease mechanism and pathways. In this review, we provide an overview of basic information about iPSCs, and discuss efforts aimed at the use of iPSC-derived hepatocytes, cardiomyocytes, and neural cells in drug discovery and toxicity testing.

The usefulness of combined anti-HCV and 24 mini-pool HCV RNA screening strategy was re-evaluated after a six-year continuous routine use in a clinical virology laboratory, at which more than half of newly diagnosed hepatitis C patients are intravenous drug users. Pools of 24 samples were prepared from 20,448 anti-HCV negative serum samples and tested using an automated commercial PCR assay with a lower limit of detection of 50 IU/ml. After detection of anti-HCV negative/HCV RNA positive patients, responsible physicians provided follow-up samples. Thirty-eight (0.19%) anti-HCV negative/HCV RNA positive samples from 30 patients (28 intravenous drug users) were detected. Follow-up samples were available for 27/30 patients. Twenty, six and one patient seroconverted in the second, third and fourth available samples, respectively. The interval between the first HCV RNA positive and the first available anti-HCV positive sample was 17-517 days. The costs of detecting a single anti-HCV negative/HCV RNA positive patient were 1227 Euros. Combined anti-HCV and 24 mini-pool HCV RNA screening is a useful and cost effective strategy, not only in blood-transfusion settings but also in a routine clinical virology laboratory, at which a significant proportion of the tested population belongs to a high-risk population.

As part of the chemical screening and prioritization research program of the US EPA, the ToxCast Phase II chemicals were assessed using a vertebrate screen for developmental toxicity. Zebrafish embryos (Danio rerio) were exposed in 96-well plates from late-blastula stage (6hr pos...

Objective New York State adopted a new HIV testing law in 2010 requiring medical providers to offer an HIV test to all eligible patients aged 13–64 years during emergency room or ambulatory care visits. Since then, Wyckoff Heights Medical Center (WHMC) in Brooklyn, New York, began implementing routine HIV screening organization-wide using a compliance, behavior-modification, and continuous quality-improvement process. Methods WHMC first implemented HIV screening in the emergency department (ED) and evaluated progress with the following monthly indicators: HIV tests offered, HIV tests accepted, HIV tests ordered (starting in December 2013), HIV tests administered, positive HIV tests, and linkage to HIV care. Compliance with the delivery of HIV testing was determined by the proportion of patients who, after accepting a test, received one. Results During August 2013 through July 2014, of 57,852 eligible patients seen in the WHMC ED, a total of 31,423 (54.3%) were offered an HIV test. Of those, 8,229 (26.2%) patients accepted a test. Of those, 6,114 (74.3%) underwent a test. A total of 26 of the 6,114 patients tested (0.4%) had a positive test, and 24 of the 26 HIV-positive patients were linked to HIV medical care. By July 2014, the monthly proportion of patients offered a test was 62%; the proportion of those offered a test who had a test ordered was 98%, and the proportion of those with a test ordered who were tested was 81%. Testing compliance increased substantially at the WHMC ED, from 77% in December 2013 to >98% in July 2014. Conclusion Using compliance-monitoring, behavior-modification, and continuous quality-improvement processes produced substantial increases in offers and HIV test completion. WHMC is replicating this approach across departments, and other hospitals implementing routine HIV screening programs should consider this approach as well. PMID:26862231

A goal of the Tox21 program is to transit toxicity testing from traditional in vivo models to in vitro assays that assess how chemicals affect cellular responses and toxicity pathways. A critical contribution of the NIH Chemical Genomics center (NCGC) to the Tox21 program is the implementation of a quantitative high throughput screening (qHTS) approach, using cell- and biochemical-based assays to generate toxicological profiles for thousands of environmental compounds. Here, we evaluated the effect of chemical compounds on mitochondrial membrane potential in HepG2 cells by screening a library of 1,408 compounds provided by the National Toxicology Program (NTP) in a qHTS platform. Compounds were screened over 14 concentrations, and results showed that 91 and 88 compounds disrupted mitochondrial membrane potential after treatment for one or five h, respectively. Seventy-six compounds active at both time points were clustered by structural similarity, producing 11 clusters and 23 singletons. Thirty-eight compounds covering most of the active chemical space were more extensively evaluated. Thirty-six of the 38 compounds were confirmed to disrupt mitochondrial membrane potential using a fluorescence plate reader and 35 were confirmed using a high content imaging approach. Among the 38 compounds, 4 and 6 induced LDH release, a measure of cytotoxicity, at 1 or 5 h, respectively. Compounds were further assessed for mechanism of action (MOA) by measuring changes in oxygen consumption rate, which enabled identification of 20 compounds as uncouplers. This comprehensive approach allows for evaluation of thousands of environmental chemicals for mitochondrial toxicity and identification of possible MOAs. PMID:23895456

The brine shrimp (Artemia salina) bioassay was used to screen 211 methanol extracts from 128 species of Pacific Northwest plants in search of general cytotoxic activity. Strong toxicity (LC50 toxicity (LC50 100-500 µg/ml) was found in 38 extracts from 27 species, while weak toxicity (LC50 500-1000 µg/ml) was detected for 17 extracts in 16 species. There were 139 extracts from 99 species that were non-toxic (LC50 > 1000 µg/ml). Our subsequent studies of conifer heartwoods with strong activity confirm the assay's value for identifying new investigational leads for materials with insecticidal and fungicidal activity.

Techniques for the field characterization of soil contamination due to spillage of hazardous waste or toxic chemicals are time-consuming and expensive. Thus more economical, less time-intensive methods are needed to facilitate rapid field screening of contaminated sites. The overall objective of this project is to study the feasibility of using an evanescent field absorbance sensor Fourier transform infrared spectroscopic sensor coupled with cone penetrometry as a field screening method. The specific objectives of this project are as follows: design an accessory for use with FT-IR that interfaces the spectrometer to a cone penetrometer; characterize the response of the FT-IR accessory to selected hydrocarbons in a laboratory-simulated field environment; and determine the ability of the FT-IR-CPT instrument to measure hydrocarbon contamination in soil by direct comparison with a reference method (e.g., Soxhlet extraction followed by gas chromatography) to quantify hydrocarbons from the same soil.

Continuing efforts to improve the University of San Francisco/NASA toxicityscreening test method have included the addition of exercise wheels to provide a different measure of incapacitation, and oxygen replenishment to offset any effect of oxygen depletion by the test animals. The addition of exercise wheels limited the number of animals in each test and doubled the required number of tests without any significant improvement in reproducibility. Oxygen replenishment appears to have an effect on survival in the last 5 minutes of the 30-minute test, but the effect is expected to be similar for most materials.

New chemicals or drugs must be guaranteed safe before they can be marketed. Despite widespread use of bioassay panels for toxicity prediction, products that are toxic to a subset of the population often are not identified until clinical trials. This article reviews new array methodologies based on enzyme/DNA films that form and identify DNA-reactive metabolites that are indicators of potentially genotoxic species. This molecularly based methodology is designed in a rapid screening array that utilizes electrochemiluminescence (ECL) to detect metabolite-DNA reactions, as well as biocolloid reactors that provide the DNA adducts and metabolites for liquid chromatography–mass spectrometry (LC-MS) analysis. ECL arrays provide rapid toxicityscreening, and the biocolloid reactor LC-MS approach provides a valuable follow-up on structure, identification, and formation rates of DNA adducts for toxicity hits from the ECL array screening. Specific examples using this strategy are discussed. Integration of high-throughput versions of these toxicity-screening methods with existing drug toxicity bioassays should allow for better human toxicity prediction as well as more informed decision making regarding new chemical and drug candidates. PMID:22482786

New chemicals or drugs must be guaranteed safe before they can be marketed. Despite widespread use of bioassay panels for toxicity prediction, products that are toxic to a subset of the population often are not identified until clinical trials. This article reviews new array methodologies based on enzyme/DNA films that form and identify DNA-reactive metabolites that are indicators of potentially genotoxic species. This molecularly based methodology is designed in a rapid screening array that utilizes electrochemiluminescence (ECL) to detect metabolite-DNA reactions, as well as biocolloid reactors that provide the DNA adducts and metabolites for liquid chromatography-mass spectrometry (LC-MS) analysis. ECL arrays provide rapid toxicityscreening, and the biocolloid reactor LC-MS approach provides a valuable follow-up on structure, identification, and formation rates of DNA adducts for toxicity hits from the ECL array screening. Specific examples using this strategy are discussed. Integration of high-throughput versions of these toxicity-screening methods with existing drug toxicity bioassays should allow for better human toxicity prediction as well as more informed decision making regarding new chemical and drug candidates.

Background Human papillomavirus (HPV) is a sexually transmitted infection that may lead to development of precancerous and cancerous lesions of the cervix. The aim of the current study was to investigate socio-demographic, lifestyle, and medical factors for potential associations with cervical HPV infection in women undergoing cervical cancer screening in Spain. Methods The CLEOPATRE Spain study enrolled 3 261 women aged 18–65 years attending cervical cancer screening across the 17 Autonomous Communities. Liquid-based cervical samples underwent cytological examination and HPV testing. HPV positivity was determined using the Hybrid Capture II assay, and HPV genotyping was conducted using the INNO-LiPA HPV Genotyping Extra assay. Multivariate logistic regression was used to identify putative risk factors for HPV infection. Results A lifetime number of two or more sexual partners, young age (18–25 years), a history of genital warts, and unmarried status were the strongest independent risk factors for HPV infection of any type. Living in an urban community, country of birth other than Spain, low level of education, and current smoking status were also independent risk factors for HPV infection. A weak inverse association between condom use and HPV infection was observed. Unlike monogamous women, women with two or more lifetime sexual partners showed a lower risk of infection if their current partner was circumcised (P for interaction, 0.005) and a higher risk of infection if they were current smokers (P for interaction, 0.01). Conclusion This is the first large-scale, country-wide study exploring risk factors for cervical HPV infection in Spain. The data strongly indicate that variables related to sexual behavior are the main risk factors for HPV infection. In addition, in non-monogamous women, circumcision of the partner is associated with a reduced risk and smoking with an increased risk of HPV infection. PMID:22734435

The thrust to streamline the Superfund site investigation/remediation program makes it critical for site investigators to utilize rapid screening methodologies to facilitate decision-making. However, screening methodologies providing information upon which decision-making is based must not only be rapid but also scientifically valid. This presentation compares and contrasts two rapid screeningtoxicity assessments, the Daphnia magna IQ Toxicity Test {trademark} and Microtox{trademark}, to a battery of standard aquatic toxicity tests using Lemna, Rana, Pimephales, Selenastruni and Ceriodaphnia. Chemical analysis of test water samples provided evidence of potential toxicological risk associated with the test samples. The study site was J-Field, Aberdeen Proving Ground, Maryland, a federal facility listed on the National Priority List that used to test and/or dispose of high explosives and chemical warfare agents in open pits or fields. Surface water samples from 20 sites were collected and used in the toxicity assessments. Water samples also were analyzed for explosives, chemical surety degradation compounds, Target Analyte List (inorganics), Target Compound List (organics) and selected pesticides and PCBs. The Microtox{trademark} assay did not reveal any toxicity present in the samples analyzed. Correlation analyses showed only slight correlation between the Daphnia magna IQ{trademark} assay and the standard 48-hour toxicity test. No correlation existed between the Microtox{trademark} assay and the aquatic toxicity tests. Results are discussed in light of the expected risk of the chemicals known to be present and the outcome of the toxicity tests.

Background: There is a need for interventions to promote uptake of breast screening throughout Europe. Methods: We performed a single-blind randomised controlled trial to test whether text-message reminders were effective. Two thousand two hundred and forty women receiving their first breast screening invitation were included in the study and randomly assigned in a 1 : 1 ratio to receive either a normal invitation only (n=1118) or a normal invitation plus a text-message reminder 48 h before their appointment (n=1122). Findings: In the intention-to-treat analysis, uptake of breast screening was 59.1% among women in the normal invitation group and 64.4% in the text-message reminder group (χ2=6.47, odds ratio (OR): 1.26, 95% confidence intervals (CI): 1.05–1.48, P=0.01). Of the 1122 women assigned to the text-message reminder group, only 456 (41%) had a mobile number recorded by their GP and were thereby sent a text. In the per-protocol analysis, uptake by those in the control group who had a mobile number recorded on the GP system was 59.77% and by those in the intervention group who were sent a reminder 71.7% (χ2=14.12, OR=1.71, 95% CI=1.29–2.26, P<0.01). Interpretation: Sending women a text-message reminder before their first routine breast screening appointment significantly increased attendance. This information can be used to allocate resources efficiently to improve uptake without exacerbating social inequalities. PMID:25668008

The mucosal microbiota lives in close proximity with the intestinal epithelium and may interact more directly with the host immune system than the luminal/fecal bacteria. The availability of nutrients in the mucus layer of the epithelium is also very different from the gut lumen environment. Inferred metagenomic analysis for microbial function of the mucosal microbiota is possible by PICRUSt. We recently found that by using this approach, actively inflamed tissue of ulcerative colitis (UC) patients have mucosal communities enriched for genes involved in lipid and amino acid metabolism, and reduced for carbohydrate and nucleotide metabolism. Here, we find that the same bacterial taxa (e.g. Acinetobacter) and predicted microbial pathways enriched in actively inflamed colitis tissue are also enriched in the mucosa of subjects undergoing routinescreening colonoscopies, when compared with paired samples of luminal/fecal bacteria. These results suggest that the mucosa of healthy individuals may be a reservoir of aerotolerant microbial communities expanded during colitis. PMID:25559083

Population-based human in vitro models offer exceptional opportunities for evaluating the potential hazard and mode of action of chemicals, as well as variability in responses to toxic insults among individuals. This study was designed to test the hypothesis that comparative population genomics with efficient in vitro experimental design can be used for evaluation of the potential for hazard, mode of action, and the extent of population variability in responses to chemical mixtures. We selected 146 lymphoblast cell lines from 4 ancestrally and geographically diverse human populations based on the availability of genome sequence and basal RNA-seq data. Cells were exposed to two pesticide mixtures - an environmental surface water sample comprised primarily of organochlorine pesticides and a laboratory-prepared mixture of 36 currently used pesticides - in concentration response and evaluated for cytotoxicity. On average, the two mixtures exhibited a similar range of in vitro cytotoxicity and showed considerable inter-individual variability across screened cell lines. However, when in vitro-to-in vivo extrapolation (IVIVE) coupled with reverse dosimetry was employed to convert the in vitro cytotoxic concentrations to oral equivalent doses and compared to the upper bound of predicted human exposure, we found that a nominally more cytotoxic chlorinated pesticide mixture is expected to have greater margin of safety (more than 5 orders of magnitude) as compared to the current use pesticide mixture (less than 2 orders of magnitude) due primarily to differences in exposure predictions. Multivariate genome-wide association mapping revealed an association between the toxicity of current use pesticide mixture and a polymorphism in rs1947825 in C17orf54. We conclude that a combination of in vitro human population-based cytotoxicity screening followed by dosimetric adjustment and comparative population genomics analyses enables quantitative evaluation of human health hazard from

Population-based human in vitro models offer exceptional opportunities for evaluating the potential hazard and mode of action of chemicals, as well as variability in responses to toxic insults among individuals. This study was designed to test the hypothesis that comparative population genomics with efficient in vitro experimental design can be used for evaluation of the potential for hazard, mode of action, and the extent of population variability in responses to chemical mixtures. We selected 146 lymphoblast cell lines from 4 ancestrally and geographically diverse human populations based on the availability of genome sequence and basal RNA-seq data. Cells were exposed to two pesticide mixtures – an environmental surface water sample comprised primarily of organochlorine pesticides and a laboratory-prepared mixture of 36 currently used pesticides – in concentration response and evaluated for cytotoxicity. On average, the two mixtures exhibited a similar range of in vitro cytotoxicity and showed considerable inter-individual variability across screened cell lines. However, when in vitroto-in vivo extrapolation (IVIVE) coupled with reverse dosimetry was employed to convert the in vitro cytotoxic concentrations to oral equivalent doses and compared to the upper bound of predicted human exposure, we found that a nominally more cytotoxic chlorinated pesticide mixture is expected to have greater margin of safety (more than 5 orders of magnitude) as compared to the current use pesticide mixture (less than 2 orders of magnitude) due primarily to differences in exposure predictions. Multivariate genome-wide association mapping revealed an association between the toxicity of current use pesticide mixture and a polymorphism in rs1947825 in C17orf54. We conclude that a combination of in vitro human population-based cytotoxicity screening followed by dosimetric adjustment and comparative population genomics analyses enables quantitative evaluation of human health hazard

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicityscreening and safety assessment of drugs, cosmetic or their specific ingredients.

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicityscreening and safety assessment of drugs, cosmetic or their specific ingredients.

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicityscreening and safety assessment of drugs, cosmetic or their specific ingredients. PMID:27653274

Introduction Hospitals conduct extensive screening procedures to assess colonisation of the body surface of neonates by gram-negative bacteria to avoid complications like late-onset sepsis. However, the benefits of these procedures are controversially discussed. Until now, no systematic review has investigated the value of routinescreening for colonisation by gram-negative bacteria in neonates for late-onset sepsis prediction. Methods and analysis We will conduct a systematic review, considering studies of any design that include infants up to an age of 12 months. We will search MEDLINE and EMBASE (inception to 2016), reference lists and grey literature. Screening of titles, abstracts and full texts will be conducted by two independent reviewers. We will extract data on study characteristics and study results. Risk of bias will be assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Quality in Prognosis Studies (QUIPS) tools. Subgroup analyses are planned according to characteristics of studies, participants, index tests and outcome. For quantitative data synthesis on prognostic accuracy, sensitivity and specificity of screening to detect late-onset sepsis will be calculated. If sufficient data are available, we will calculate summary estimates using hierarchical summary receiver operating characteristics and bivariate models. Applying a risk factor approach, pooled summary estimates will be calculated as relative risk or OR, using fixed-effects and random-effects models. I-squared will be used to assess heterogeneity. All calculations will be performed in Stata V14.1 (College Station, Texas, USA). The results will be used to calculate positive and negative predictive value and number needed to be screened to prevent one case of sepsis. Grading of Recommendations Assessment, Development and Evaluation (GRADE) will be used to assess certainty in the evidence. The protocol follows the Preferred Reporting Items for Systematic Review and

Continuing efforts to increase the versatility of the USF/NASA toxicityscreening test method have included the use of different test conditions in order to simulate various fire environments. The use of air flow at flow rates of 16 to 48 ml/sec maintains oxygen concentrations above 19 percent throughout the 30 min exposure period, compared to above 16 percent without forced air flow. These levels of oxygen are well within the tolerance range of mice, and approach the oxygen levels found in many real fire situations. Proposed minimum oxygen levels based on experience with rats are unduly restrictive on the use of other species such as mice, and tend to eliminate the cost savings which may more than justify the selection of mice.

Novel spheroid-type tumor cell cultures directly isolated from patients' tumors preserve tumor characteristics better than traditionally grown cell lines. However, such cultures are not generally used for high-throughput toxicity drug screens. In addition, the assays that are commonly used to assess drug-induced toxicity in such screens usually measure a proxy for cell viability such as mitochondrial activity or ATP-content per culture well, rather than actual cell death. This generates considerable assay-dependent differences in the measured toxicity values. To address this problem we developed a robust method that documents drug-induced toxicity on a per-cell, rather than on a per-well basis. The method involves automated drug dispensing followed by paired image- and FACS-based analysis of cell death and cell cycle changes. We show that the two methods generate toxicity data in 96-well format which are highly concordant. By contrast, the concordance of these methods with frequently used well-based assays was generally poor. The reported method can be implemented on standard automated microscopes and provides a low-cost approach for accurate and reproducible high-throughput toxicityscreens in spheroid type cell cultures. Furthermore, the high versatility of both the imaging and FACS platforms allows straightforward adaptation of the high-throughput experimental setup to include fluorescence-based measurement of additional cell biological parameters.

Bisphenol A (BPA) acts as an endocrine-disrupting compound even at a low concentration. Degradation of BPA could lead to the formation of toxic products. In this study, we compare the toxicity of BPA and seven intermediate products of its degradation. The accuracy of three molecular docking programs (Surflex, Autodock, and Autodock Vina) in predicting the binding affinities of selected compounds to human (ERα, ERβ, and ERRγ) and zebrafish (ERα, ERRγA, and ERRγB) estrogen and estrogen-related receptors was evaluated. The docking experiments showed that 4-isopropylphenol could have similar toxicity to that of BPA due to its high affinity to ERRγ and ERRγB and high octanol-water partitioning coefficient. The least toxic compounds were hydroquinone and phenol. Those compounds as well as BPA were screened in the zebrafish (Danio rerio) embryo test. 4-isopropylphenol had the strongest toxic effect on zebrafish embryos and caused 100% lethality shortly after exposure. BPA caused the delay in development, multiple deformations, and low heartbeats (30 bps), whereas hydroquinone had no impact on the development of the zebrafish embryo. Thus, the results of zebrafish screening are in good agreement with our docking experiment. The molecular docking could be used to screen the toxicity of other xenoestrogens and their products of degradation.

Early diagnosis of human immunodeficiency virus (HIV) infection and initiation of antiretroviral treatment (ART) improves health outcomes and prevents HIV transmission. Before 2010, HIV testing was available to inmates in the California state prison system upon request. In 2010, the California Correctional Health Care Services (CCHCS) integrated HIV opt-out screening into the health assessment for inmates entering California state prisons. Under this system, a medical care provider informs the inmate that an HIV test is routinely done, along with screening for sexually transmitted, communicable, and vaccine-preventable diseases, unless the inmate specifically declines the test. During 2012-2013, CCHCS, the California Department of Public Health, and CDC evaluated HIV screening, rates of new diagnoses, linkage to and retention in care, ART response, and post-release linkage to care among California prison inmates. All prison inmates are processed through one of eight specialized reception center facilities, where they undergo a comprehensive evaluation of their medical needs, mental health, and custody requirements for placement in one of 35 state prisons. Among 17,436 inmates who entered a reception center during April-September 2012, 77% were screened for HIV infection; 135 (1%) tested positive, including 10 (0.1%) with newly diagnosed infections. Among the 135 HIV-positive patient-inmates, 134 (99%) were linked to care within 90 days of diagnosis, including 122 (91%) who initiated ART. Among 83 who initiated ART and remained incarcerated through July 2013, 81 (98%) continued ART; 71 (88%) achieved viral suppression (<200 HIV RNA copies/mL). Thirty-nine patient-inmates were released on ART; 12 of 14 who were linked to care within 30 days of release were virally suppressed at that time. Only one of nine persons with a viral load test conducted between 91 days and 1 year post-release had viral suppression. Although high rates of viral suppression were achieved in

Addressing the safety aspects of drugs and environmental chemicals has historically been undertaken through animal testing. However, the quantity of chemicals in need of assessment and the challenges of species extrapolation require the development of alternative approaches. Our approach, the US Environmental Protection Agency's ToxCast program, utilizes a large suite of in vitro and model organism assays to interrogate important chemical libraries and computationally analyze bioactivity profiles. Here we evaluated one component of the ToxCast program, the use of primary human cell systems, by screening for chemicals that disrupt physiologically important pathways. Chemical-response signatures for 87 endpoints covering molecular functions relevant to toxic and therapeutic pathways were generated in eight cell systems for 641 environmental chemicals and 135 reference pharmaceuticals and failed drugs. Computational clustering of the profiling data provided insights into the polypharmacology and potential off-target effects for many chemicals that have limited or no toxicity information. The endpoints measured can be closely linked to in vivo outcomes, such as the upregulation of tissue factor in endothelial cell systems by compounds linked to the risk of thrombosis in vivo. Our results demonstrate that assaying complex biological pathways in primary human cells can identify potential chemical targets, toxicological liabilities and mechanisms useful for elucidating adverse outcome pathways.

Capecitabine, 5-fluorouracil and tegafur form the group called the fluoropyrimidines, which is one of the most frequently prescribed group of anti-cancer drugs for the treatment of (metastatic) colorectal, gastric and breast cancer. The primary enzyme responsible for the inactivation of the fluoropyrimidines is dihydropyrimidine dehydrogenase (DPD). Consequently, patients with an inborn partial DPD deficiency, induced, for example by the polymorphism DPYD*2A, are highly prone to severe, potentially lethal toxicity following a standard dose of fluoropyrimidines. In this article, based on three representative case reports and our prospective study in patients with cancer, we demonstrate the clinical value of prospective screening for DPD deficiency in patients being treated with fluoropyrimidine-based anti-cancer therapy. The results show that upfront genotyping for DPYD*2A followed by a fluoropyrimidine dose reduction of 50% (on average) in patients heterozygous polymorphic for DPYD*2A, significantly reduces the incidence of severe to potentially lethal toxicity compared to historical control patients given full-dose therapy.

Naphthenic acids (NAs) are primarily cycloaliphatic carboxylic acids with 10 to 16 carbons. To characterize the potential of refined NAs (>70% purity) to cause reproductive and/or developmental effects, Sprague-Dawley rats (12/group) were given oral doses of 100, 300, or 900 mg/kg/d, beginning 14 days prior to mating, then an additional 14 days for males or through lactation day 3 for females (up to 53 days) in a repeated dose/reproductive toxicity test (Organization for Economic Cooperation and Development [OECD] 422). Potential mutagenic effects were assessed using Salmonella (OECD 471) and in in vivo micronucleus tests (OECD 474) using bone marrow taken from treated animals in the screening study described previously. Systemic effects included reduced terminal body weights, increased liver weights, and changes in a number of blood cell parameters. The overall no effect level for all target organ effects was 100 mg/kg/d. In the reproductive/developmental toxicity assessment, there were significant reductions in numbers of live born offspring in groups exposed to 300 and 900 mg/kg/d. The overall no effect level for developmental effects was 100 mg/kg/d. The data from the Salmonella and micronucleus tests provide evidence that refined NAs are not genotoxic.

Electronic waste has become one of the fastest growing waste problems in the world. It contains both toxic metals and toxic organics. The aim of this study was to (1) investigate to what extent toxicants can leach from different electronic products, components, and materials into water and (2) identify which group of toxicants (metals or hydrophobic organics) that is causing toxicity. Components from five discarded electronic products (cell phone, computer, phone modem, keyboard, and computer mouse) were leached in deionised water for 3 days at 23°C in concentrations of 25 g/l for metal components, 50 g/l for mixed-material components, and 100 g/l for plastic components. The water phase was tested for acute toxicity to Daphnia magna. Eighteen of 68 leachates showed toxicity (with immobility of D. magna ≥ 50% after 48 h) and came from metal or mixed-material components. The 8 most toxic leachates, with 48 h EC(50)s ranging from 0.4 to 20 g/l, came from 2 circuit sheets (key board), integrated drive electronics (IDE) cable clips (computer), metal studs (computer), a circuit board (computer mouse), a cord (phone modem), mixed parts (cell phone), and a circuit board (key board). All 5 electronic products were represented among them. Toxicity identification evaluations (with C18 and CM resins filtrations and ethylenediaminetetraacetic acid addition) indicated that metals caused the toxicity in the majority of the most toxic leachates. Overall, this study has shown that electronic waste can leach toxic compounds also during short-term leaching with pure water.

Routine DNA testing. It’s done once you’ve Marker-Assisted Breeding Pipelined promising Qantitative Trait Loci within your own breeding program and thereby established the performance-predictive power of each DNA test for your germplasm under your conditions. By then you are ready to screen your par...

Current National Comprehensive Cancer Network guidelines for breast cancer staging include pre-treatment complete blood count (CBC) and liver function tests (LFT) to screen for occult metastatic disease. To date, the relevance of these tests in detecting metastatic disease in asymptomatic women with early-stage breast cancer (Stage I/II) has not been demonstrated. Although chest x-rays are no longer recommended in the NCCN guidelines, many centers continue to include this imaging as part of their screening process. We aim to determine the clinical and financial impact of these labs and x-rays in the evaluation of early-stage breast cancer patients. A single institution IRB-approved retrospective chart review was conducted of patients with biopsy-proven invasive breast cancer treated from January 1, 2005–December 31, 2009. We collected patient demographics, clinical and pathologic staging, chest x-ray, CBC, and LFT results at the time of referral. Patients were stratified according to radiographic stage at the time of diagnosis. We obtained Medicare reimbursement fees for cost analysis. From 2005 to 2009, 1609 patients with biopsy-proven invasive breast cancer were treated at our institution. Of the 1082 patients with radiographic stage I/II disease, 27.3 % of patients had abnormal CBCs. No additional testing was performed to evaluate these abnormalities. In the early-stage population, 24.7 % of patients had elevated LFTs, resulting in 84 additional imaging studies. No metastatic disease was detected. The cost of CBC, LFTs and chest x-rays was $110.20 per patient, totaling $106,410.99. Additional tests prompted by abnormal results cost $58,143.30 over the five-year period. We found that pre-treatment CBCs, LFTs, and chest x-rays did not improve detection of occult metastatic disease but resulted in additional financial costs. Avoiding routine ordering of these tests would save the US healthcare system $25.7 million annually.

Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans (Presented by James McKim, Ph.D., DABT, Founder and Chief Science Officer, CeeTox) (5/25/2012)

Nanoparticles (NPs) are novel materials having at least one dimension less than 100 nm and display unique physicochemical properties due to their nanoscale size. An emphasis has been placed on developing high throughput screening (HTS) assays to characterize and rank the toxiciti...

Techniques for the field characterization of soil contamination due to spillage of hazardous waste or toxic chemicals are time consuming and expensive. Thus more economical, less time intensive methods are needed to facilitate rapid field screening of contaminated sites. In situ detection of toxic chemicals in soil offers both time and cost advantages for field screening, with additional application to real time site monitoring.

One sample each of commercial polyurethane and polychloroprene flexible foams were evaluated using the USF/NASA toxicityscreening test method. Air flow rates of 0, 0.16, 16, and 48 ml/sec were used to determine the effect of air flow on relative toxicity. Time to first sign of incapacitation and time to death were substantially reduced with both polyurethane and polychloroprene flexible foams by the introduction of 16 to 48 ml/sec air flow. The relative toxicity rankings of these materials were not altered by changes in air flow. Under these test conditions, the polyurethane foam consistently appeared more toxic than the polychloroprene foam. Samples of six different colors from the same fabric were evaluated separately, using the USF/NASA toxicityscreening test method, to determine the effect of fabric dye, if any. The material was an upholstery fabric, consisting of 46 percent cotton, 33 percent wool, and 21 percent nylon. There appeared to be no significant effect of fabric dye on relative toxicity, for this material under these test conditions.

Plasticizers are indispensable additives providing flexibility and malleability to plastics. Among them, several phthalates, including di (2-ethylhexyl) phthalate (DEHP), have emerged as endocrine disruptors, leading to their restriction in consumer products and creating a need for new, safer plasticizers. The goal of this project was to use in vitro functional screening tools to select novel non-toxic plasticizers suitable for further in vivo evaluation. A panel of novel compounds with satisfactory plasticizer properties and biodegradability were tested, along with several commercial plasticizers, such as diisononyl-cyclohexane-1,2-dicarboxylate (DINCH®). MEHP, the monoester metabolite of DEHP was also included as reference compound. Because phthalates target mainly testicular function, including androgen production and spermatogenesis, we used the mouse MA-10 Leydig and C18-4 spermatogonial cell lines as surrogates to examine cell survival, proliferation, steroidogenesis and mitochondrial integrity. The most promising compounds were further assessed on organ cultures of rat fetal and neonatal testes, corresponding to sensitive developmental windows. Dose-response studies revealed the toxicity of most maleates and fumarates, while identifying several dibenzoate and succinate plasticizers as innocuous on Leydig and germ cells. Interestingly, DINCH®, a plasticizer marketed as a safe alternative to phthalates, exerted a biphasic effect on steroid production in MA-10 and fetal Leydig cells. MEHP was the only plasticizer inducing the formation of multinucleated germ cells (MNG) in organ culture. Overall, organ cultures corroborated the cell line data, identifying one dibenzoate and one succinate as the most promising candidates. The adoption of such collaborative approaches for developing new chemicals should help prevent the development of compounds potentially harmful to human health.

Alzheimer's disease (AD) is characterized by neuronal and synaptic loss. One process that could contribute to this loss is the intracellular caspase cleavage of the amyloid precursor protein (APP) resulting in release of the toxic C-terminal 31-amino acid peptide APP-C31 along with the production of APPΔC31, full-length APP minus the C-terminal 31 amino acids. We previously found that a mutation in APP that prevents this caspase cleavage ameliorated synaptic loss and cognitive impairment in a murine AD model. Thus, inhibition of this cleavage is a reasonable target for new therapeutic development. In order to identify small molecules that inhibit the generation of APP-C31, we first used an APPΔC31 cleavage site-specific antibody to develop an AlphaLISA to screen several chemical compound libraries for the level of N-terminal fragment production. This antibody was also used to develop an ELISA for validation studies. In both high throughput screening (HTS) and validation testing, the ability of compounds to inhibit simvastatin- (HTS) or cerivastatin- (validation studies) induced caspase cleavage at the APP-D720 cleavage site was determined in Chinese hamster ovary (CHO) cells stably transfected with wildtype (wt) human APP (CHO-7W). Several compounds, as well as control pan-caspase inhibitor Q-VD-OPh, inhibited APPΔC31 production (measured fragment) and rescued cell death in a dose-dependent manner. The effective compounds fell into several classes including SERCA inhibitors, inhibitors of Wnt signaling, and calcium channel antagonists. Further studies are underway to evaluate the efficacy of lead compounds - identified here using cells and tissues expressing wt human APP - in mouse models of AD expressing mutated human APP, as well as to identify additional compounds and determine the mechanisms by which they exert their effects.

Alzheimer’s disease (AD) is characterized by neuronal and synaptic loss. One process that could contribute to this loss is the intracellular caspase cleavage of the amyloid precursor protein (APP) resulting in release of the toxic C-terminal 31-amino acid peptide APP-C31 along with the production of APPΔC31, full-length APP minus the C-terminal 31 amino acids. We previously found that a mutation in APP that prevents this caspase cleavage ameliorated synaptic loss and cognitive impairment in a murine AD model. Thus, inhibition of this cleavage is a reasonable target for new therapeutic development. In order to identify small molecules that inhibit the generation of APP-C31, we first used an APPΔC31 cleavage site-specific antibody to develop an AlphaLISA to screen several chemical compound libraries for the level of N-terminal fragment production. This antibody was also used to develop an ELISA for validation studies. In both high throughput screening (HTS) and validation testing, the ability of compounds to inhibit simvastatin- (HTS) or cerivastatin- (validation studies) induced caspase cleavage at the APP-D720 cleavage site was determined in Chinese hamster ovary (CHO) cells stably transfected with wildtype (wt) human APP (CHO-7W). Several compounds, as well as control pan-caspase inhibitor Q-VD-OPh, inhibited APPΔC31 production (measured fragment) and rescued cell death in a dose-dependent manner. The effective compounds fell into several classes including SERCA inhibitors, inhibitors of Wnt signaling, and calcium channel antagonists. Further studies are underway to evaluate the efficacy of lead compounds – identified here using cells and tissues expressing wt human APP – in mouse models of AD expressing mutated human APP, as well as to identify additional compounds and determine the mechanisms by which they exert their effects. PMID:28261092

This study was carried out in the framework of the ICON project (Integrated Assessment of Contaminant Impacts on the North Sea) (Hylland et al., 2015) and aimed (1) to evaluate the toxicity of marine sediments using a battery of rapid toxicity bioassays, and; (2) to explore the applicability and data interpretation of in vitro toxicity profiling of sediment extracts obtained from ex situ passive sampling. Sediment samples were collected at 12 selected (estuarine, coastal, offshore) sites in the North Sea, Icelandic waters (as reference sites), south-western Baltic Sea and western Mediterranean during autumn 2008. Organic extracts using a mild non-destructive clean-up procedure were prepared from total sediment and silicone passive samplers and tested with five in vitro bioassays: DR-Luc bioassay, ER-Luc bioassay, AR-EcoScreen bioassay, transthyretin (TTR) binding assay, and Vibrio fischeri bioluminescence bioassay. In vitro toxicity profiling of total sediment and silicone passive sampler extracts showed the presence of multiple organic contaminations by arylhydrocarbon receptor agonists (e.g. polycyclic aromatic hydrocarbons) and endocrine-active compounds, as well as non-specific toxicity caused by organic contaminants, at virtually all sampling sites. In vitro responses to total sediment extracts from coastal/estuarine sites were significantly different from those in offshore sites (p toxicity profiles could only partially be explained by the chemical target analysis, indicating the presence of unknown or unanalysed biologically-active compounds in the sediments. In vitro bioassay testing with silicone passive sampler extracts of sediments is a promising tool to assess the toxic

In 2007, the United States Food and Drug Administration released guidance recommending testing of glycerin used in regulated consumer products, such as cough syrup preparations, toothpaste, and other pharmaceutical and food products, for the toxic compounds ethylene glycol and diethylene glycol. Regulatory laboratories routinely test glycerin, and products containing glycerin or related compounds for these toxic glycols, using an official gas chromatographic method, to ensure the safety of these products. The current work describes a companion technique to compliment this GC-FID method utilizing Orbitrap mass spectrometry with direct analysis in real time ionization to rapidly screen these samples qualitatively, with results in as little as five seconds, with no sample preparation required. This allows the more time and resource intensive method to be reserved for those rare cases when these compounds are detected, potentially greatly improving laboratory efficiency. The technique was evaluated for qualitative sensitivity and repeatability, and compared against the GC-FID method. The method appears to perform well against these metrics.

Paper and board used as food contact materials (FCMs) are chemically complex matrices, partly due to the naturally occurring substances in paper and board, but also due to the chemical treatment of the paper used to make it suitable for food contact. In order to assure the safety of packaging materials, information on the exposure as well as on the toxicity of substances in the packaging must be obtained. This study describes a comprehensive method for the extraction and fractionation of substances present in paper and board FCMs for further investigation by in vitro testing and chemical analysis. The extraction efficiency and the fractionation process were validated by determining recoveries in extracts from paper and board fortified with five surrogates of known concentration. The recoveries for the five surrogates were between 20% and 104% in the raw extract and between 21% and 109% after extraction and fractionation. The fractionation both reduces the number of compounds to be identified and works as a sample clean-up by reducing matrix effects. Raw extracts and fractions from two paper and board FCMs were furthermore tested in the aryl hydrocarbon receptor (AhR) reporter gene assay. Both raw extracts and two of the fractions of the raw extracts gave a positive response in the AhR assay. The strategy of extraction followed by fractionation offers a powerful tool in order to make the workflow for screening FCMs for potentially adverse effects more efficient.

A broad patient-completed screening tool in routine clinical practice in head and neck oncology has merit, but clinicians should be aware that its simplicity could lead to some patients and the detail of their problems being missed. The purpose of this study was to compare the University of Washington Quality of Life (UWQoL) swallowing domain with the MD Anderson Dysphagia Inventory (MDADI) in relation to the need for interventions for swallowing around one year after treatment. The group comprised 112 consecutively referred patients to speech and language therapy between January 2007 and August 2009 after primary operation for previously untreated oral and oropharyngeal squamous cell carcinoma (SCC). A total of 78 patients completed questionnaires (median time of assessment 11.7 months, IQR 6.1-12.2). There were significant (p<0.001) and moderately strong correlations (rs=0.51-0.62) between the UWQoL swallowing domain score and MDADI subscales and total scores, and also with individual MDADI questions: taking a great deal of effort (rs=0.71); being upset (rs=0.61); and not going out (rs=0.62) were the strongest in regard to swallowing. Use of a gastrostomy tube was associated with worse UWQoL and MDADI scores. In conclusion, patients who score 100 on the UWQoL do not require swallowing to be evaluated further. Those who score 70 could benefit from the detailed MDADI to help to clarify the specific problem and the impact it has before being referred to speech and language therapy. Those who score less than 70 should be brought to the attention of speech and language therapists to confirm that appropriate support and intervention are in place.

A simple screening method served to detect beta-lactam antibiotic-tolerant variants of clinical isolates and laboratory control strains of staphylococcus aureus, S. epidermis, group B beta-hemolytic streptococci, and Listeria monocytogenes. The beta-lactamase(s) of a multiple drug-resistant strain of Enterobacter cloacae (isolate No. 19) yielded most consistent results as compared with several other beta-lactamase producers; the E. cloacae beta-lactamase(s) was neutralized by clavulanic acid. Spot inocula of E. cloacae isolate No. 19, following overnight "induction" with 1 microgram/ml of ampicillin and 3 microgram/ml of cephalothin in tryptic soya broth, were applied centrally to beta-lactam antibiotic inhibition zones of Bauer-Kirby antibiogram plates (Mueller-Hinton agar, MHA, and diagnostic sensitivity test agar, DSTA) following removal of the appropriate disks. The spot-inoculated plates were incubated overnight at 35 degrees C and inspected for satellite growths of tolerant variants around the E. cloacae spot inocula. Satellite growths of less than or equal to 10 colonies were interpreted to indicate tolerance of the relevant cell wall synthesis inhibitor. The method readily permitted detection of variants tolerant for ampicillin, cephalothin, penicillin G, piperacillin, azlocillin, and mezlocillin. However, strains documented by minimal inhibitory and minimal bactericidal concentrations to be tolerant for cefotaxime, cefoxitin, fosfomycin, and vancomycin only rarely gave rise to respective satellite growths. DSTA proved superior to MHA with respect to "rescue" of inhibited tolerant staphylococcal variants; furthermore, the diameters of inhibition zones obtained on DSTA correlated well with those on MHA. Therefore, DSTA was adopted as the routine test medium for clinical staphylococcal isolates.

In addition to molecular structure profiles, descriptors based on physicochemical properties are useful for explaining the eco-toxicities of chemicals. In a previous study we reported that a criterion based on the difference between the partition coefficient (log POW) and distribution coefficient (log D) values of chemicals enabled us to identify aromatic amines and phenols for which interspecies relationships with strong correlations could be developed for fish-daphnid and algal-daphnid toxicities. The chemicals that met the log D-based criterion were expected to have similar toxicity mechanisms (related to membrane penetration). Here, we investigated the applicability of log D-based criteria to the eco-toxicity of other kinds of chemicals, including aliphatic compounds. At pH 10, use of a log POW - log D > 0 criterion and omission of outliers resulted in the selection of more than 100 chemicals whose acute fish toxicities or algal growth inhibition toxicities were almost equal to their acute daphnid toxicities. The advantage of log D-based criteria is that they allow for simple, rapid screening and prioritizing of chemicals. However, inorganic molecules and chemicals containing certain structural elements cannot be evaluated, because calculated log D values are unavailable.

Recent advances in liquid chromatography/tandem mass spectrometry (LC/MS/MS) technology have provided an opportunity for the development of more specific approaches to achieve the 'screen' and 'confirmation' goals in a single analytical step. For this purpose, this study adapts the electrospray ionization ion trap LC/MS/MS instrumentation (LC/ESI-MS/MS) for the screening and confirmation of over 800 drugs and toxic compounds in biological specimens. Liquid-liquid and solid-phase extraction protocols were coupled to LC/ESI-MS/MS using a 1.8-microm particle size analytical column operated at 50 degrees C. Gradient elution of the analytes was conducted using a solvent system composed of methanol and water containing 0.1% formic acid. Positive-ion ESI-MS/MS spectra and retention times for each of the 800 drugs and toxic compounds were first established using 1-10 microg/mL standard solutions. This spectra and retention time information was then transferred to the library and searched by the identification algorithm for the confirmation of compounds found in test specimens - based on retention time matches and scores of fit, reverse fit, and purity resulting from the searching process. The established method was found highly effective when applied to the analyses of postmortem specimens (blood, urine, and hair) and external proficiency test samples provided by the College of American Pathology (CAP). The development of this approach has significantly improved the efficiency of our routine laboratory operation that was based on a two-step (immunoassay and GC/MS) approach in the past.

Semipermeable membrane devices (SPMDs) were deployed for 4 weeks in two rivers in Lithuania, The SPMD dialysates were tested in the Microtox assay and, surprisingly, the sample from the relatively clean (U) over bar la River exhibited three times more toxicity than the sample fro...

Survey information on pesticide usage in New Zealand during 1985-1989 is summarized by regions and principal applications. Two screening tests, one based on a simple water-balance method and the other based on a semiempirical runoff formula, have been used to identify 18 pesticides with application rates that may yield runoff concentrations that are harmful to aquatic fauna. These are predominantly associated either with intensive applications in horticulture or extensive applications to cereal crops and pasture. The purpose of the screening tests was to calculate typical edge-of-field concentrations in runoff and, by comparing them with known aquatic toxicity values, determine which compounds are applied at rates that may yield toxic runoff. While it may be possible to extend these methods to calculate typical surface water concentrations, further studies will be needed to evaluate pesticide persistence and assimilation in stream channels.

The utility of a fish DNA damage assay as a rapid monitoring tool was investigated. Metal plating wastewater was chosen as a sample because it contains various genotoxic metal species. Fish DNA damage assay results were compared to data generated from the conventional whole effluent toxicity (WET) test procedure. The Microtox{reg_sign} assay (Azur Environmental, Carlsbad, CA, USA) using Vibrio fischeri was also employed. Eleven samples from two metal plating companies were collected for this evaluation. For the fish DNA damage assay, 7-d-old fathead minnow larvae, Pimephales promelas, were utilized. They were exposed to a series of dilutions at 20 C for 2 h. Whole effluent toxicity tests conducted in this study included two acute toxicity tests with Daphnia magna and fathead minnows and two chronic toxicity tests with Ceriodaphnia dubia and fathead minnows. The fish DNA damage assay showed good correlations with both the acute and chronic WET test results, especially with those obtained with fathead minnows. The kappa values, an index of agreement, between the fish DNA damage assay and WET tests were shown to be acceptable. These findings imply that this novel fish DNA damage assay has use as an expedient toxicityscreening procedure since it produces comparable results to those of the acute and chronic fathead minnow toxicity tests.

Humans are exposed to a variety of potential developmental toxicants. This fact, combined with the knowledge that human development can be disrupted by "environmental" agents, has led to the development of methods designed to identify potential developmental toxicants. Currently, the principal method used to screen drugs and chemicals that are potential human developmental toxicants is the segment II study (i.e., a study in which prospective drugs and chemicals are tested in pregnant animals). Because of the cost and time involved in such studies and the pressure to reduce the number of animals used in such testing, alternative methods for developmental toxicity testing have been sought. This has resulted in a number of in vitro tests whose aim is to screen large numbers of agents quickly and inexpensively. Although numerous in vitro tests of developmental toxicity have been developed during the last 15 years, no one system or combination of tests have been validated for the purpose intended. Nonetheless, two systems--the limb bud/CNS micromass, and the chick embryo neural retina cell culture (CERC)--continue to be advanced as viable in vitro developmental toxicology tests. The purpose of this commentary is to evaluate the prospects for the development of an in vitro test system(s) that can screen the universe of drugs and chemicals and reliably identify those that require further study and those that do not. The conclusion of this investigator is that the prospects for validating such in vitro tests are not promising. This conclusion is based primarily on the lack of basic knowledge regarding the relevance of end points assayed in the micromass and CERC test systems to those end points known or thought to be critical for normal development.

Early life-stage bioassays have been used as an alternative to short-term adult toxicity tests since they are cost-effective. A single couple can produce hundreds or thousands of embryos and hence can be used as a simple high-throughput approach in toxicity studies. In the present study, zebrafish and sea urchin embryo bioassays were used to test the toxicity of four pharmaceuticals belonging to different therapeutic classes: diclofenac, propranolol, simvastatin and sertraline. Simvastatin was the most toxic tested compound for zebrafish embryo, followed by diclofenac. Sertraline was the most toxic drug to sea urchin embryos, inducing development abnormalities at the ng/L range. Overall, our results highlight the potential of sea urchin embryo bioassay as a promising and sensitive approach for the high-throughput methods to test the toxicity of new chemicals, including pharmaceuticals, and identify several drugs that should go through more detailed toxicity assays.

Due to poor drug candidate safety profiles that are often identified late in the drug development process, the clinical progression of new chemical entities to pharmaceuticals remains hindered, thus resulting in the high cost of drug discovery. To accelerate the identification of safer drug candidates and improve the clinical progression of drug candidates to pharmaceuticals, it is important to develop high-throughput tools that can provide early-stage predictive toxicology data. In particular, in vitro cell-based systems that can accurately mimic the human in vivo response and predict the impact of drug candidates on human toxicology are needed to accelerate the assessment of drug candidate toxicity and human metabolism earlier in the drug development process. The in vitro techniques that provide a high degree of human toxicity prediction will be perhaps more important in cosmetic and chemical industries in Europe, as animal toxicity testing is being phased out entirely in the immediate future. We have developed a metabolic enzyme microarray (the Metabolizing Enzyme Toxicology Assay Chip, or MetaChip) and a miniaturized three-dimensional (3D) cell-culture array (the Data Analysis Toxicology Assay Chip, or DataChip) for high-throughput toxicityscreening of target compounds and their metabolic enzyme-generated products. The human or rat MetaChip contains an array of encapsulated metabolic enzymes that is designed to emulate the metabolic reactions in the human or rat liver. The human or rat DataChip contains an array of 3D human or rat cells encapsulated in alginate gels for cell-based toxicityscreening. By combining the DataChip with the complementary MetaChip, in vitro toxicity results are obtained that correlate well with in vivo rat data. PMID:20217581

The U.S. Tox21 collaborative program represents a paradigm shift in toxicity testing of chemical compounds from traditional in vivo tests to less expensive and higher throughput in vitro methods to prioritize compounds for further study, identify mechanisms of action, and ultimately develop predictive models for adverse health effects in humans. The NIH Chemical Genomics Center (NCGC) is an integral component of the Tox21 collaboration due to its quantitative high throughput screening (qHTS) paradigm, in which titration-based screening is used to profile hundreds of thousands of compounds per week. Here, we describe the Tox21 collaboration, qHTS-based compound testing, and the various Tox21 screening assays that have been validated and tested at the NCGC to date. PMID:20708096

U.S. regulatory agencies commonly require effluent toxicity testing with Ceriodaphnia dubia- a practice which has led to the criticism that this species and test protocol often does not reflect local taxa nor site-specific conditions. Using an indigenous test species may produce a more realistic model of local effects and may minimize test endpoint variance due to regional differences in water quality. This study addressed the substitution of C. dubia with Daphnia ambigua for toxicity testing in the southeastern United States. This investigation determined that D. ambigua could be laboratory cultured with only minimal changes to established regulatory protocol, and that the life-cycle characteristics of this species were conducive to traditional acute and chronic aquatic toxicity test methods used with other daphnids. Acute toxicity tests showed that D. ambigua was less sensitive to some toxicants (sodium chloride, copper sulfate, and sodium lauryl sulfate) yet more sensitive to others (chlorpyrifos). Chronic tests with copper sulfate and sodium chloride resulted in lower EC50s for D. ambigua reproduction with both compounds. When exposed to low-alkalinity, low-pH stream waters typical of many southeastern United States watersheds, C. dubia demonstrated a significant reproductive depression in two of three streams tested, while D. ambigua experienced no chronic effect. These results suggest that D. ambigua may serve as a suitable surrogate for C. dubia as an toxicity indicator species in these types of receiving streams.

U.S. regulatory agencies commonly require effluent toxicity testing with Ceriodaphnia dubia--a practice that has led to the criticism that this species and test protocol often does not reflect local taxa or site-specific conditions. Using an indigenous test species may produce a more realistic model of local effects and may minimize test endpoint variance due to regional differences in water quality. This study addressed the substitution of C. dubia with Daphnia ambigua for toxicity testing in the southeastern United States. This investigation determined that D. ambigua could be laboratory cultured with only minimal changes to established regulatory protocol and that the life-cycle characteristics of this species were conducive to traditional acute and chronic aquatic toxicity test methods used with other daphnids. Acute toxicity tests showed that D. ambigua was less sensitive to some toxicants (sodium chloride, copper sulfate, and sodium lauryl sulfate) but more sensitive to others (chlorpyrifos). Chronic tests with copper sulfate and sodium chloride resulted in lower EC50S for D. ambigua reproduction with both compounds. When exposed to low-alkalinity, low-pH stream waters typical of many southeastern United States watersheds, C. dubia demonstrated a significant reproductive depression in two of three streams tested, whereas D. ambigua experienced no chronic effect. These results suggest that D. ambigua may serve as a suitable surrogate for C. dubia as an toxicity indicator species in these types of receiving streams.

The results from the screeningtoxicity tests Artemia salina, Microtox{reg_sign}, and Mitochondria RET test were compared with those obtained from OSPAR (Oslo and Paris Commissions)-authorized procedures for testing of offshore chemicals (Skeletonema costatum, Acartia tonsa, Abra alba, and Corophium volutator). In this study 82 test substances (26 non-water soluble) were included. The Microtox test was found to be the most sensitive of the three screening tests. Microtox and Mitochondria RET test results showed good correlation with results from Acartia and Skeletonema testing, and it was concluded that the Microtox test was a suitable screening test as a base for assessment of further testing, especially regarding water-soluble chemicals. Sensitivity of Artemia salina to the tested chemicals was too low for it to be an appropriate bioassay organism for screening testing. A very good correlation was found between the results obtained with the Skeletonema and Acartia tests. The results indicated no need for more than one of the Skeletonema or Acartia tests if the Skeletonema median effective concentration or Acartia median lethal concentration was greater than 200 mg/L. The sediment-reworker tests (A. Alba or C. volutator) for chemicals that are likely to end up in the sediments (non-water soluble or surfactants) should be performed, independent of results from screening tests and other OSPAR species.

There continue to be widespread efforts to develop assay methods for developmental toxicity that are shorter than the traditional Segment 2 study and use fewer or no animals. As with any alternative test method, novel developmental toxicity assays must be validated by evaluating ...

The National Research Council of the United States National Academies of Science has recently released a document outlining a long-range vision and strategy for transforming toxicity testing from largely whole animal-based testing to one based on in vitro assays. “Toxicity Testin...

A time-integrated sampling system interfaced with a toxicity-based assay is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethyl sulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor...

EPA's ToxCast™ project is profiling the in vitro bioactivity of chemicals to assess pathway-level and cell-based signatures that correlate with observed in vivo toxicity. We hypothesized that developmental toxicity in guideline animal studies captured in the ToxRefDB database wou...

Chemical perturbation of vascular development is a putative toxicity pathway which may result in developmental toxicity. EPA’s high-throughput screening (HTS) ToxCast program contains assays which measure cellular signals and biological processes critical for blood vessel develop...

This pilot study aimed to test four substance use screening devices developed in Germany under local South African conditions and assess their utility for detecting driving under the influence of drugs (DUID) as part of the standard roadblock operations of local law enforcement agencies. The devices were used to screen a sample of motorists in the Gauteng and Western Cape provinces. The motorists were diverted for screening at roadblocks at the discretion of the law enforcement agencies involved, as per their standard operating procedures. Fieldworkers also administered a questionnaire that described the screening procedure, as well as information about vehicles, demographic information about the motorists and their attitudes to the screening process during testing. Motorists tested positive for breath alcohol in 28% of the 261 cases tested. Oral fluid was screened for drugs as per the standard calibrated cut-offs of all four devices. There were 14 cases where the under-influence drivers tested positive for alcohol and drugs simultaneously, but 14% of the 269 drivers drug-screened tested positive for drugs only. After alcohol, amphetamine, methamphetamine and cocaine were the most common drugs of impairment detected. The results suggest that under normal enforcement procedures only 76% of drivers impaired by alcohol and other drugs would have been detected. In more than 70% of cases the tests were administered within 5 min and this is likely to improve with more regular use. It was clear that the pilot screening process meets global testing standards. Although use of the screening devices alone would not serve as a basis for prosecution and provisions would need to be made for the confirmation of results through laboratory testing, rollout of this screening process would improve operational efficiency in at least two ways. Firstly, the accuracy of the tests will substantially decrease confirmatory test loads. Secondly, laboratory drug testing can be restricted to

Mangroves represent areas of high biological productivity and it is a region rich in bioactive substances used in medicine production. Conocarpus erectus (Combretaceae) known as button mangrove is one of the species found in mangroves and it is used in folk medicine in the treatment of anemia, catarrh, conjunctivitis, diabetes, diarrhea, fever, gonorrhea, headache, hemorrhage, orchitis, rash, bumps and syphilis. The present study aimed to investigate the acute toxicity of aqueous extract of leaves of C. erectus in Swiss albino mice. The plant material was collected in Vila Velha mangroves, located in Itamaracá (PE). The material was subjected to a phytochemical screening where extractive protocols to identify majority molecules present in leaves were used. The evaluation of acute toxicity of aqueous extract of C. erectus followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001. The majority molecules were identified: flavonoids, tannins and saponins. The LD50 was estimated at 2,000 mg/kg bw. Therefore, the aqueous extract showed low acute toxicity classified in category 5.

An in vitro test system is described which allows for quick and relatively inexpensive examination of the potential for chemical toxicity to the pulp of materials and procedures used in the restoration of single teeth. The test system consisted of two sequential steps. First, a restorative procedure was carried out on a freshly-extracted human tooth crown, to the pulpal surface of which had been attached a chamber filled with sterile tissue-culture medium. The preparation was kept at 37 degrees C. The culture medium was removed at day one and replaced with fresh medium, which was removed at day 3. In the second step, we used a standard tissue-culture toxicity assessment technique to examine both culture medium samples for the presence of chemical toxins. In use, this system gave results which correlated well with the known clinical potential for pulpal toxicity of various dental materials and techniques. For example, zinc oxide-eugenol used as temporary filling or base had no apparent potential for toxicity. Sealing a cotton pellet containing phenol into a cavity was of high apparent potential toxicity. Acrylic resin as intracoronal or extracoronal fillings showed potential for toxicity; this potential was decreased by lining with calcium hydroxide cement. Composite resin placed onto etched dentin had apparent toxic potential, but had less such potential when placed onto unetched dentin. The technique had some advantages over previously described in vitro toxicity test for restorative materials, because it included a step requiring diffusion of potential toxins into and through human dentin, and because it allowed for examination of variations in technique which mimic clinical behavior, and of materials used in sequence or in combination.

The authors tested five composite soil samples from a former refinery. The samples included a reference soil (Mineral Oil and Grease, MO and G < 40 ppm), thermally-treated soil, biotreated soil, and two untreated soils. They evaluated toxicity using the earthworm E. foetida, lettuce, cress, barley, Microtox, green algae, fathead minnow, and D. magna. The endpoints measured were lethality, seed germination, root elongation, growth, and bioluminescence. Toxicity, as measured by the number of positive responses, increased as follows: biotreated soil < untreated soil No. 1 < reference soil < thermally-treated soil and untreated soil No. 2. The biotreated soil generated only one positive response, whereas the thermally-treated soil and untreated soil No. 2 generated five positive responses. The most sensitive and discriminant terrestrial endpoint was lettuce root elongation which responded to untreated soil No. 1, thermally-treated soil, and reference soil. The least sensitive was barley seed germination for which no toxicity was detected. The most sensitive and discriminant aquatic endpoint was green algae growth which responded to untreated soil No. 1, thermally-treated soil, and reference soil. The least sensitive was D. magna for which no toxicity was detected. Overall, soil and aqueous extract toxicity was spotty and no consistent patterns emerged to differentiate the five soils. Biotreatment significantly reduced the effects of the contamination. Aqueous toxicity was measured in the reference soil, probably because of the presence of unknown dissolved compounds in the aqueous extract. Finally, clear differences in sensitivity existed among the test species.

Hypertension is a leading risk factor in the global disease burden. Limited hypertension awareness is a major determinant of widespread gaps in hypertension treatment and control, especially in developing countries. We analyzed data on persons aged 50 years or older from 6 low- and middle-income countries participating in the first wave (2007-2010) of the World Health Organization's Survey of Global Ageing and Adult Health (SAGE). Our estimates suggest that just 1 year of routine opportunistic hypertension screening during formal visits to medical-care providers could yield significant increases in hypertension awareness among seniors in the developing world. We also show that eliminating missed opportunities for hypertension screening in medical settings would not necessarily exacerbate existing socioeconomic differences in hypertension awareness, despite requiring at least occasional contact with a formal health-care provider for obtaining a hypertension diagnosis. Thus, routine opportunistic screening for hypertension in formal medical settings may provide a simple but reliable way to increase hypertension awareness. Moreover, the proposed approach has the added advantage of leveraging existing resources and infrastructures, as well as facilitating a direct transition from the point of diagnosis to subsequent expert counseling and clinical care for newly identified hypertension patients.

Efficient environment protection and human safety require high-throughput analysis techniques for pollutants or toxicants for large sample sets. State-of-the-art HPLC and GC coupled to various detecting strategies offer excellent sensitivity and selectivity, though they are quite time-extensive (2 - 3 samples/h or less when sample preparation is involved). Efforts are made towards screening techniques with high sample throughputs simultaneously providing detection limits below the maximum contaminant levels for the analyte. However, such approaches frequently sacrifice the selectivity or sensitivity (or just give a yes/no response). In this review, we demonstrate thermal-lens spectrometry and microscopy as highly sensitive spectrometric techniques in combination with flow-injection analysis (FIA) and microfluidic FIA along with lab-on-a-chip chemistry for fast screening (several samples/h and up to 20 samples/min) exemplified by organophosphates and carbamates as neurotoxigenic compounds. Various approaches to determining other topical toxicants, like microcystin and cyanopigments as its indicators, allergens, and carcinogenic chromate, are also discussed.

Since 2007, the U.S. Food and Drug Administration (FDA) has received numerous complaints of pet illnesses that may be related to the consumption of jerky pet treats. Many of those treats include glycerin as an ingredient. Glycerin can be made directly from oils such as palm seed oil, but can also be derived from the seed oil of toxic Jatropha plant during biodiesel production. If crude glycerin from biodiesel production from Jatropha curcas is used in the manufacture of animal feed, toxic tigliane diterpene phorbol esters (PEs), namely Jatropha factors (JFs), may be present and could lead to animal illnesses. Considering the numerous uses of glycerin in consumer products there is a need for a rapid method to screen crude glycerin for JF toxins and other PE contaminants. We describe the development of an ultra-high pressure liquid chromatography/quadrupole time of flight (UHPLC/Q-TOF) method for screening crude glycerin for PEs. An exact mass database, developed in-house, of previously identified PEs from Jatropha curcas as well as putative compounds was used to identify possible contaminants.

Current high-throughput approaches evaluating toxicity of chemical agents toward bacteria typically rely on optical assays, such as luminescence and absorbance, to probe the viability of the bacteria. However, when applied to toxicity induced by nanomaterials, scattering and absorbance from the nanomaterials act as interferences that complicate quantitative analysis. Herein, we describe a bacterial viability assay that is free of optical interference from nanomaterials and can be performed in a high-throughput format on 96-well plates. In this assay, bacteria were exposed to various materials and then diluted by a large factor into fresh growth medium. The large dilution ensured minimal optical interference from the nanomaterial when reading optical density, and the residue left from the exposure mixture after dilution was confirmed not to impact the bacterial growth profile. The fractions of viable cells after exposure were allowed to grow in fresh medium to generate measurable growth curves. Bacterial viability was then quantitatively correlated to the delay of bacterial growth compared to a reference regarded as 100% viable cells; data analysis was inspired by that in quantitative polymerase chain reactions, where the delay in the amplification curve is correlated to the starting amount of the template nucleic acid. Fast and robust data analysis was achieved by developing computer algorithms carried out using R. This method was tested on four bacterial strains, including both Gram-negative and Gram-positive bacteria, showing great potential for application to all culturable bacterial strains. With the increasing diversity of engineered nanomaterials being considered for large-scale use, this high-throughput screening method will facilitate rapid screening of nanomaterial toxicity and thus inform the risk assessment of nanoparticles in a timely fashion.

The Society of Toxicologic Pathology charged a Nervous System Sampling Working Group with devising recommended practices to routinelyscreen the central and peripheral nervous systems in Good Laboratory Practice-type nonclinical general toxicity studies. Brains should be trimmed ...

Screening of pharmaceutical, chemical, and environmental compounds for their effects on reproductive health relies on in vivo studies. More robust and efficient methods to assess thes effects are needed. Here we adapted and validated an organotypic in vitro follicle growth (IVFG) assay to determine the impact of compounds on markers of ovarian function. We isolated mammalian follicles and cultured them in the presence of compounds with 1) known fertotoxicity (i.e., toxicity to the reproductive system; cyclophosphamide and cisplatin); 2) no known fertotoxicity (nalbuphine); and 3) unknown fertotoxicity (Corexit EC 9500 A; CE). In each case we assayed follicle growth, hormone production, and the ability of follicle-enclosed oocytes to resume meiosis and produce a mature egg. We found that cyclophosphamide and cisplatin caused dose-dependent disruption of follicle dynamics, whereas nalbuphine did not. The reproductive toxicity of CE, an oil dispersant used heavily during the 2010 Deepwater Horizon oil spill, has never been examined in a mammalian system. We found that CE compromised follicle morphology and functional parameters. Our findings demonstrate that this IVFG assay system can be used to distinguish fertotoxic from non-toxic compounds, providing an in vitro tool for assessing effects of chemical compounds on reproductive function and health. PMID:25689754

Cyanobacteria are a diverse group of Gram-negative bacteria that produce an array of secondary compounds with selective bioactivity against vertebrates, invertebrates, plants, microalgae, fungi, bacteria, viruses and cell lines. The aim of this study was to assess the toxic effects of aqueous, methanolic and hexane crude extracts of benthic and picoplanktonic cyanobacteria isolated from estuarine environments, towards the nauplii of the brine shrimp Artemia salina and embryos of the sea urchin Paracentrotus lividus. The A. salina lethality test was used as a frontline screen and then complemented by the more specific sea urchin embryo-larval assay. Eighteen cyanobacterial isolates, belonging to the genera Cyanobium, Leptolyngbya, Microcoleus, Phormidium, Nodularia, Nostoc and Synechocystis, were tested. Aqueous extracts of cyanobacteria strains showed potent toxicity against A. salina, whereas in P. lividus, methanolic and aqueous extracts showed embryo toxicity, with clear effects on development during early stages. The results suggest that the brackishwater cyanobacteria are producers of bioactive compounds with toxicological effects that may interfere with the dynamics of invertebrate populations.

Cyanobacteria are a diverse group of Gram-negative bacteria that produce an array of secondary compounds with selective bioactivity against vertebrates, invertebrates, plants, microalgae, fungi, bacteria, viruses and cell lines. The aim of this study was to assess the toxic effects of aqueous, methanolic and hexane crude extracts of benthic and picoplanktonic cyanobacteria isolated from estuarine environments, towards the nauplii of the brine shrimp Artemia salina and embryos of the sea urchin Paracentrotus lividus. The A. salina lethality test was used as a frontline screen and then complemented by the more specific sea urchin embryo-larval assay. Eighteen cyanobacterial isolates, belonging to the genera Cyanobium, Leptolyngbya, Microcoleus, Phormidium, Nodularia, Nostoc and Synechocystis, were tested. Aqueous extracts of cyanobacteria strains showed potent toxicity against A. salina, whereas in P. lividus, methanolic and aqueous extracts showed embryo toxicity, with clear effects on development during early stages. The results suggest that the brackishwater cyanobacteria are producers of bioactive compounds with toxicological effects that may interfere with the dynamics of invertebrate populations. PMID:20411110

Ecological Soil Screening Levels (Eco-SSLs) protective of terrestrial wildlife were developed by the USEPA Superfund. The wildlife Eco-SSL is the soil contaminant concentration where the Effect Dose (TRV) and Exposure Dose are equal (amount of contaminant in the diet that is take...

Abstract

The objective of this study was to screen and select biologically-compatible surfactants for subsequent use in enhancing the bioavailability and reductive dechlorination of sorbed-phase chlorinated organic contaminants. Sixteen surfactants commonly used in sur...

The U.S. Environmental Protection Agency is screening large numbers of chemicals using 6 day old zebrafish (Danio rerio). We use a behavioral testing paradigm that simultaneously tests individual zebrafish under both light and dark conditions in a 96-well plate using a video tr...

Many chemicals in commerce today have undergone limited or no safety testing. To reduce the number of untested chemicals and prioritize limited testing resources, several governmental programs are using high-throughput in vitro screens for assessing chemical effects across multip...

Chemical screening in the United States is often conducted using scoring and ranking methodologies. Linked models accounting for chemical fate, exposure, and toxicological effects are generally preferred in Europe and in product Life Cycle Assessment. For the first time, a compar...

The risk assessment of contaminated soils is conventionally done with the support of soil screening values (SSVs). Since SSVs are still unavailable for many European countries, including Portugal, standardized toxicity tests are urgently claimed for their derivation. Hence, this work aimed the generation of toxicity values for copper (Cu) in a natural reference soil (PTRS1) targeting different terrestrial species, endpoints and soil functions, as to derive a preliminary Cu SSV. For this, the Assessment Factor approach was applied, which allowed calculating predicted no effect concentrations (PNEC) for Cu that will be the basis for SSV proposal. In order to increase the reliability of the PNEC, and hence of the SSV, a lab/field factor was applied to correct the toxicity values used for PNEC determination. Cu affected urease, cellulase and nitrogen mineralization activities. The EC50 values calculated for the invertebrates reproduction were 130.9, 165.1 and 191.6 mg Cu Kg(-1) soildw for Eisenia andrei, Enchytraeus crypticus and Folsomia candida, respectively. Cu inhibited seed germination mainly for Lactuca sativa, whilst it was toxic for the growth of different plant species (EC50s between 89 and 290.5 mg Cu Kg(-1) soildw). Based on the outcomes gathered, we proposed SSVs for Cu ranging between 26.3 and 31.8 mg Kg(-1) soildw, which is above the background values reported and below all the EC20s recorded for the species and endpoints herein analyzed. Overall, this work describes a procedure that could be easily followed by other European countries wishing to derive SSVs adjusted to their soils.

We show that in vitro toxicity assay based on inhibition of the bioluminescence of recombinant Escherichia coli encoding thermostable luciferase from Photorhabdus luminescens is a versatile alternative to Vibrio fischeri Microtox™ test. Performance of two luxCDABE-transformed E. coli MC1061 constructs (pDNlux) and (pSLlux) otherwise identical, but having 100-fold different background luminescence was compared with the performance of V. fischeri. The microplate luminometer and a kinetic Flash-Assay test format was used that differently from Microtox test is also applicable for high throughput analysis. Toxic effects (30-s till 30-min EC50) of four heavy metals (Zn, Cd, Hg, Cu) and three organic chemicals (aniline, 3,5-dichloroaniline and 3,5-dichlorophenol) were studied. Both E. coli strains had comparable sensitivity and the respective 30-min EC50 values highly correlated (log-log R2 = 0.99; p < 0.01) showing that the sensitivity of the recombinant bacteria towards chemicals analyzed did not depend on the bioluminescence level of the recombinant cells. The most toxic chemical for all used bacterial strains (E. coli, V. fischeri) was mercury whereas the lowest EC50 values for Hg (0.04–0.05 mg/L) and highest EC50 values for aniline (1,300–1,700 mg/L) were observed for E. coli strains. Despite of that, toxicity results obtained with both E. coli strains (pSLlux and pDNlux) significantly correlated with V. fischeri results (log-log R2 = 0.70/0.75; p < 0.05/0.01). The use of amino acids (0.25%) and glucose (0.05%)-supplemented M9 medium instead of leucine-supplemented saline significantly (p < 0.05) reduced the apparent toxicity of heavy metals to both E. coli strains up to three orders of magnitude, but had little or no complexing effect on organic compounds. Thus, P. luminescens luxCDABE-transformed E. coli strains can be successfully used for the acute toxicityscreening of various types of organic chemicals and heavy metals and can replace V. fischeri in

Recently, several emerging pollutants, including Personal Care Products (PCPs), have been detected in aquatic ecosystems, in the ng/L or µg/L range. Available toxicological data is limited, and, for certain PCPs, evidence indicates a potential risk for the environment. Hence, there is an urgent need to gather ecotoxicological data on PCPs as a proxy to improve risk assessment. Here, the toxicity of three different PCPs (4-Methylbenzylidene Camphor (4-MBC), propylparaben and triclocarban) was tested using embryo bioassays with Danio rerio (zebrafish) and Paracentrotus lividus (sea urchin). The No Observed Effect Concentration (NOEC) for triclocarban was 0.256 µg/L for sea urchin and 100 µg/L for zebrafish, whereas NOEC for 4-MBC was 0.32 µg/L for sea urchin and 50 µg/L for zebrafish. Both PCPs impacted embryo development at environmentally relevant concentrations. In comparison with triclocarban and 4-MBC, propylparaben was less toxic for both sea urchin (NOEC = 160 µg/L) and zebrafish (NOEC = 1000 µg/L). Overall, this study further demonstrates the sensitivity of embryo bioassays as a high-throughput approach for testing the toxicity of emerging pollutants.

Recently, several emerging pollutants, including Personal Care Products (PCPs), have been detected in aquatic ecosystems, in the ng/L or µg/L range. Available toxicological data is limited, and, for certain PCPs, evidence indicates a potential risk for the environment. Hence, there is an urgent need to gather ecotoxicological data on PCPs as a proxy to improve risk assessment. Here, the toxicity of three different PCPs (4-Methylbenzylidene Camphor (4-MBC), propylparaben and triclocarban) was tested using embryo bioassays with Danio rerio (zebrafish) and Paracentrotus lividus (sea urchin). The No Observed Effect Concentration (NOEC) for triclocarban was 0.256 µg/L for sea urchin and 100 µg/L for zebrafish, whereas NOEC for 4-MBC was 0.32 µg/L for sea urchin and 50 µg/L for zebrafish. Both PCPs impacted embryo development at environmentally relevant concentrations. In comparison with triclocarban and 4-MBC, propylparaben was less toxic for both sea urchin (NOEC = 160 µg/L) and zebrafish (NOEC = 1000 µg/L). Overall, this study further demonstrates the sensitivity of embryo bioassays as a high-throughput approach for testing the toxicity of emerging pollutants. PMID:27775672

The term Java tea refers to the decoction of Orthosiphon stamineus (OS) Benth (Lamiaceae) leaves, which are widely consumed by the people in Europe and South East Asian countries. The OS leaves are known for their use in traditional medicinal systems as a prophylactic and curative agent for urinary stone, diabetes, and hypertension and also as a diuretic agent. The present study was aimed at evaluating its possible toxicity. Herein, the major phytochemical constituents of microwave dried OS leaf, which is the common drying process for tea sachets in the market, were also identified. The acute oral toxicity test of aqueous, 50% aqueous ethanolic, and ethanolic extracts of OS was performed at a dose of 5000 mg/Kg body weight of Sprague-Dawley rats. During the 14-day study, the animals were observed for any mortality, behavioral, motor-neuronal abnormalities, body weight, and feed-water consumption pattern. The hematological and serum biochemical parameters to assess the kidney and liver functions were carried out, along with the histological analysis of these organs. It was found that all microwave dried OS leaf extracts did not cause any toxic effects or mortality at the administered dose. No abnormality was noticed in all selected parameters in rats of both sexes as compared with their respective control groups. Thus, the possible oral lethal dose for microwave dried Java tea leaves is more than 5000 mg/Kg body weight. PMID:26819955

Screening and pre-emptive isolation of at-risk patients are important aspects of the Danish approach to the prevention of meticillin-resistant Staphylococcusaureus (MRSA) infection, but screening with conventional culture can take up to 3 days for results to become available with attendant costs and disadvantages of prolonged isolation. We sought to evaluate the accuracy, time to availability of results and potential economic benefits of two next-generation MRSA screening assays, Xpert MRSA Gen 3 (GX MRSA) and BD MAX MRSA XT, in a setting of a consolidated laboratory serving a number of hospitals with a low prevalence of MRSA and using enrichment culture as a reference method. Four hundred and forty-seven screening samples together with 49 previously positive MRSA samples were evaluated. Xpert MRSA Gen 3 demonstrated sensitivity, specificity, positive predictive value and negative predictive value of 88.2, 97.9, 62.5 and 99.5 %, respectively, and for BD MAX MRSA XT, they were 88.2, 97.4, 57.7 and 99.5 %, respectively. Hands-on time was 8.8 and 21.6 min, respectively, for the Xpert MRSA Gen 3 and BD MAX MRSA XT PCR assays when five samples were handled simultaneously. The mean laboratory turnaround time was 2.9 (1-6) hours for the Xpert MRSA Gen 3 assay, 6.5 (2-46) hours for BD MAX MRSA XT and 49.6 (42-122) hours for enriched culture. Despite laboratory costs being higher for the rapid PCR assays, when the costs of isolation are taken into account, the assays offer the potential for significant cost savings.

Background According to some studies, almost 40% of depressive patients – half of them previously undetected – are diagnosed of bipolar II disorder when systematically assessed for hypomania. Thus, instruments for bipolar disorder screening are needed. The Mood Disorder Questionnaire (MDQ) is a self-reported questionnaire validated in Spanish in stable patients with a previously known diagnosis. The purpose of this study is to evaluate in the daily clinical practice the usefulness of the Spanish version of the MDQ in depressive patients. Methods Patients (n = 87) meeting DSM-IV-TR criteria for a major depressive episode, not previously known as bipolar were included. The affective module of the Structured Clinical Interview (SCID) was used as gold standard. Results MDQ screened 24.1% of depressive patients as bipolar, vs. 12.6% according to SCID. For a cut-off point score of 7 positive answers, sensitivity was 72.7% (95% CI = 63.3 – 82.1) and specificity 82.9% (95% CI = 74.9–90.9). Likelihood ratio of positive and negative tests were 4,252 y 0,329 respectively. Limitations The small sample size reduced the power of the study to 62%. Conclusion Sensitivity and specificity of the MDQ were high for screening bipolar disorder in patients with major depression, and similar to the figures obtained in stable patients. This study confirms that MDQ is a useful instrument in the daily clinical assessment of depressive patients. PMID:18498637

During routine testing of civilian applicants for U.S. military service, the overall seroprevalence of antibodies to HIV-1 was lower in 2010 than in any year since 1990. Among members of the active components of the U.S. Army and Air Force, HIV-1 seroprevalences were higher in 2008-2010 than in recent prior years. Among members of the active components of the U.S. Navy and Marine Corps, the Marine Corps Reserve, and the Army National Guard, HIV-1 seroprevalences have slightly declined or remained relatively stable for at least ten years. In the reserve components of most of the service branches, it is difficult to discern long-term trends because of instability of seroprevalences observed in the relatively small numbers of reserve component members tested each year.

The aim of this study was to investigate the potential toxicity of Silica nanoparticles (SiO2 NPs) in seawater by using the sea urchin Paracentrotus lividus as biological model. SiO2 NPs exposure effects were identified on the sperm of the sea urchin through a multidisciplinary approach, combining developmental biology, ecotoxicology, biochemistry, and microscopy analyses. The following responses were measured: (i) percentage of eggs fertilized by exposed sperm; (ii) percentage of anomalies and undeveloped embryos and larvae; (iii) enzyme activity alterations (acetylcholinesterase, AChE) in the early developmental stages, namely gastrula and pluteus. Sperms were exposed to seawater containing SiO2 NPs suspensions ranging from 0.0001mg/L to 50mg/L. Fertilization ability was not affected at any concentration, whereas a significant percentage of anomalies in the offspring were observed and quantified by means of EC50 at gastrula stage, including undeveloped and anomalous embryos (EC50=0.06mg/L), and at pluteus stage, including skeletal anomalies and delayed larvae (EC50=0.27mg/L). Moreover, morphological anomalies were observed in larvae at pluteus stage, by immunolocalizing molecules involved in larval development and neurotoxicity effects - such as acetylated tubulin and choline acetyltransferase (ChAT) - and measuring AChE activity. Exposure of sea urchins to SiO2 NPs caused neurotoxic damage and a decrease of AChE expression in a non-dose-dependent manner. In conclusion, through the multidisciplinary approach used in this study SiO2 NPs toxicity in sea urchin offspring could be assessed. Therefore, the measured responses are suitable for detecting embryo- and larval- toxicity induced by these NPs.

static 96-hour LC50 was determined inL i Ptmephales promelas and a 48-hour EC50 in Daphnia magna . These data, first summarized by earson et al., 31 are...of the nine chemicals. A comparison of the bacterial ECSO values and the toxic response in minnows (96-hour LCSO) and daphnia (48-hour EC5O) did not...result in a high degree of correspondence. Thus, i t was concluded that the photobacterlal test system was not highly predictive of minnow or daphnia

Setting Primary health services in Cape Town, South Africa where the introduction of Xpert® MTB/RIF (Xpert) enabled simultaneous screening for tuberculosis (TB) and drug susceptibility in all presumptive cases. Study aim To compare the proportion of TB cases with drug susceptibility tests undertaken and multidrug-resistant tuberculosis (MDR-TB) diagnosed pre-treatment and during the course of 1st line treatment in the previous smear/culture and the newly introduced Xpert-based algorithms. Methods TB cases identified in a previous stepped-wedge study of TB yield in five sub-districts over seven one-month time-points prior to, during and after the introduction of the Xpert-based algorithm were analysed. We used a combination of patient identifiers to identify all drug susceptibility tests undertaken from electronic laboratory records. Differences in the proportions of DST undertaken and MDR-TB cases diagnosed between algorithms were estimated using a binomial regression model. Results Pre-treatment, the probability of having a DST undertaken (RR = 1.82)(p<0.001) and being diagnosed with MDR-TB (RR = 1.42)(p<0.001) was higher in the Xpert-based algorithm than in the smear/culture-based algorithm. For cases evaluated during the course of 1st-line TB treatment, there was no significant difference in the proportion with DST undertaken (RR = 1.02)(p = 0.848) or MDR-TB diagnosed (RR = 1.12)(p = 0.678) between algorithms. Conclusion Universal screening for drug susceptibility in all presumptive TB cases in the Xpert-based algorithm resulted in a higher overall proportion of MDR-TB cases being diagnosed and is an important strategy in reducing transmission. The previous strategy of only screening new TB cases when 1st line treatment failed did not compensate for cases missed pre-treatment. PMID:28199375

Relative toxicity tests were performed on a polyurethane foam containing a trimethylopropane-based polyol and an organophosphate flame retardant. The routinescreening procedure involved the exposure of four Swiss albino male mice in a 4.2 liter hemispherical chamber to the products generated by pyrolyzing a 1.00 g sample at a heating rate of 40 deg C/min from 200 to 800 C in the absence of air flow. In addition to the routinescreening, experiments were performed with a very rapid rise to 800 C, with nominal 16 and 48 ml/sec air flow and with varying sample rates. No unusual toxicity was observed with either gradual or rapid pyrolysis to 800 C. Convulsions and seizures similar to those previously reported were observed when the materials were essentially flash pyrolyzed at 800 C in the presence of air flow, and the toxicity appeared unusual because of low sample weights required to produce death.

Copper-indium-gallium-selenium-sulfide (CIGS) thin film photovoltaics are increasingly penetrating the market supply for consumer solar panels. Although CIGS is attractive for producing less greenhouse gas emissions than fossil-fuel based energy sources, CIGS manufacturing processes and solar cell devices use hazardous materials that should be carefully considered in evaluating and comparing net environmental benefits of energy products. Through this research, we present a case study on the toxicity hazards associated with alternative materials selection for CIGS manufacturing. We applied two numeric models, The Green Screen for Safer Chemicals and the Toxic Potential Indicator. To improve the sensitivity of the model outputs, we developed a novel, life cycle thinking based hazard assessment method that facilitates the projection of hazards throughout material life cycles. Our results show that the least hazardous CIGS solar cell device and manufacturing protocol consist of a titanium substrate, molybdenum metal back electrode, CuInS₂ p-type absorber deposited by spray pyrolysis, ZnS buffer deposited by spray ion layer gas reduction, ZnO:Ga transparent conducting oxide (TCO) deposited by sputtering, and the encapsulant polydimethylsiloxane.

High-throughput screening (HTS) of environmental chemicals is used to identify chemicals with high potential for adverse human health and environmental effects from among the thousands of untested chemicals. Predicting physiologically relevant activity with HTS data requires estimating the response of a large number of chemicals across a battery of screening assays based on sparse dose-response data for each chemical-assay combination. Many standard dose-response methods are inadequate because they treat each curve separately and under-perform when there are as few as 6-10 observations per curve. We propose a semiparametric Bayesian model that borrows strength across chemicals and assays. Our method directly parametrizes the efficacy and potency of the chemicals as well as the probability of response. We use the ToxCast data from the U.S. Environmental Protection Agency (EPA) as motivation. We demonstrate that our hierarchical method provides more accurate estimates of the probability of response, efficacy, and potency than separate curve estimation in a simulation study. We use our semiparametric method to compare the efficacy of chemicals in the ToxCast data to well-characterized reference chemicals on estrogen receptor α (ERα) and peroxisome proliferator-activated receptor γ (PPARγ) assays, then estimate the probability that other chemicals are active at lower concentrations than the reference chemicals.

Engine technology modifications designed to reduce engine emissions are likely to alter the physicochemical characteristics of the emissions. These changes may alter the biological effects of the emissions, but these effects cannot currently be predicted from the physical and chemical properties. Rapid in vitro toxicityscreening techniques to compare the biological effects of emission samples would be useful as preliminary guides to assess the relative health impact of modified technology. Here, we demonstrate that selected responses of cultured human lung epithelial cells and rat alveolar macrophages can discriminate among combined particulate matter (PM) and semivolatile organic compound (SVOO fractions of emissions collected from normal- and high-emitter, in-use gasoline and diesel vehicles. Macrophages were more susceptible to cytotoxicity than epithelial cells. Samples from gasoline vehicles (except a vehicle that produced visible white smoke) generally caused greater effects than the diesel engine samples. However, low concentrations of diesel emission samples were more potent stimulators of peroxide production than gasoline emission samples. The same rank order of potency applied to suppression of this response at high concentrations. A diesel PM fraction was much less toxic to both types of cells than the combined PM +SVOC fractions, consistent with a role for the SVOC fraction in cytotoxicity. However, the rank order of potency from the in vitro assays in general did not correspond with the previous rankings from in vivo comparisons of the same samples. Thus, while the in vitro assays may provide mechanistic information, revealing cell type-specific responses, they did not accurately reflect in vivo comparative toxicity in their current form.

The two UV screens 3-benzylidene-camphor (3-BC) and 3-(4'-methylbenzylidene)-camphor (4-MBC) were tested regarding their toxicity and estrogenic activity. The Yeast Estrogen Screen (YES) and two sediment assays with the freshwater invertebrates Lumbriculus variegatus and Potamopyrgus antipodarum were performed. In the YES, both substances activated the human estrogen receptor alpha with EC50 values of 44.2 microM for 3-BC and 44.3 microM for 4-MBC, whereby 4-MBC attained only 8% of the maximal response of 17beta-estradiol. For P. antipodarum embryo production increased after exposure to both substances (EC50 of 4.60 microM 4-MBC=1.17 mg kg(-1)dw) while mortality increased at high concentrations. The reproduction of L. variegatus was decreased by 3-BC with an EC50 of 5.95 microM (=1.43 mg kg(-1)dw) and also by 4-MBC, where no EC50 could be calculated. While reproduction decreased, the worms' weight increased after exposure to 3-BC with an EC50 of 26.9 microM (=6.46 mg kg(-1) dw), hence the total biomass remained unaffected.

According to the US Food and Drugs Administration (Food and Drug Administration (2004) Challenge and opportunity on the critical path to new medical products.) "The inability to better assess and predict product safety leads to failures during clinical development and, occasionally, after marketing". This increases the cost of new drugs as clinical trials are even more expensive than pre-clinical testing.One relatively easy way of improving toxicity testing is to improve the design of animal experiments. A fundamental principle when designing an experiment is to control all variables except the one of interest: the treatment. Toxicologist and pharmacologists have widely ignored this principle by using genetically heterogeneous "outbred" rats and mice, increasing the chance of false-negative results. By using isogenic (inbred or F1 hybrid, see Note 1) rats and mice instead of outbred stocks the signal/noise ratio and the power of the experiments can be increased at little extra cost whilst using no more animals. Moreover, the power of the experiment can be further increased by using more than one strain, as this reduces the chance of selecting one which is resistant to the test chemical. This can also be done without increasing the total number of animals by using a factorial experimental design, e.g. if the ten outbred animals per treatment group in a 28-day toxicity test were replaced by two animals of each of five strains (still ten animals per treatment group) selected to be as genetically diverse as possible, this would increase the signal/noise ratio and power of the experiment. This would allow safety to be assessed using the most sensitive strain.Toxicologists should also consider making more use of the mouse instead of the rat. They are less costly to maintain, use less test substance, there are many inbred and genetically modified strains, and it is easier to identify gene loci controlling variation in response to xenobiotics in this species.We demonstrate

Ecological soil-screening levels (Eco-SSLs) were developed by the United States Environmental Protection Agency (USEPA) for the purposes of setting conservative soil screening values that can be used to eliminate the need for further ecological assessment for specific analytes at a given site. Ecological soil-screening levels for wildlife represent a simplified dietary exposure model solved in terms of soil concentrations to produce exposure equal to a no-observed-adverse-effect toxicity reference value (TRV). Sensitivity analyses were performed for 6 avian and mammalian model species, and 16 metals/metalloids for which Eco-SSLs have been developed. The relative influence of model parameters was expressed as the absolute value of the range of variation observed in the resulting soil concentration when exposure is equal to the TRV. Rank analysis of variance was used to identify parameters with greatest influence on model output. For both birds and mammals, soil ingestion displayed the broadest overall range (variability), although TRVs consistently had the greatest influence on calculated soil concentrations; bioavailability in food was consistently the least influential parameter, although an important site-specific variable. Relative importance of parameters differed by trophic group. Soil ingestion ranked 2nd for carnivores and herbivores, but was 4th for invertivores. Different patterns were exhibited, depending on which parameter, trophic group, and analyte combination was considered. The approach for TRV selection was also examined in detail, with Cu as the representative analyte. The underlying assumption that generic body-weight-normalized TRVs can be used to derive protective levels for any species is not supported by the data. Whereas the use of site-, species-, and analyte-specific exposure parameters is recommended to reduce variation in exposure estimates (soil protection level), improvement of TRVs is more problematic.

Ecological soil-screening levels (Eco-SSLs) were developed by the United States Environmental Protection Agency (USEPA) for the purposes of setting conservative soil screening values that can be used to eliminate the need for further ecological assessment for specific analytes at a given site. Ecological soil-screening levels for wildlife represent a simplified dietary exposure model solved in terms of soil concentrations to produce exposure equal to a no-observed-adverse-effect toxicity reference value (TRV). Sensitivity analyses were performed for 6 avian and mammalian model species, and 16 metals/metalloids for which Eco-SSLs have been developed. The relative influence of model parameters was expressed as the absolute value of the range of variation observed in the resulting soil concentration when exposure is equal to the TRV. Rank analysis of variance was used to identify parameters with greatest influence on model output. For both birds and mammals, soil ingestion displayed the broadest overall range (variability), although TRVs consistently had the greatest influence on calculated soil concentrations; bioavailability in food was consistently the least influential parameter, although an important site-specific variable. Relative importance of parameters differed by trophic group. Soil ingestion ranked 2nd for carnivores and herbivores, but was 4th for invertivores. Different patterns were exhibited, depending on which parameter, trophic group, and analyte combination was considered. The approach for TRV selection was also examined in detail, with Cu as the representative analyte. The underlying assumption that generic body-weight–normalized TRVs can be used to derive protective levels for any species is not supported by the data. Whereas the use of site-, species-, and analyte-specific exposure parameters is recommended to reduce variation in exposure estimates (soil protection level), improvement of TRVs is more problematic. Environ Toxicol Chem 2014

A simple and complete multiresidue method has been developed for the routine determination of 236 pesticides and degradation products, in meat based baby-food. This original approach combines a modified Quick Easy Cheap Effective Rugged and Safe (QuEChERS) sample preparation method using a triple partitioning extraction step with water/ACN/hexane and a system composed of GC with programmable temperature vaporization injector hyphenated to an IT-MS. Detection was performed in full scan mode, with one quantification ion and one identification ion. We firstly report here the hexane addition in the extraction step to eliminate a major part of lipophile co-extracts. Direct consequences were the increasing of method sensitivity and the diminishment of the frequency of maintenance of the analytical instrument. The recovery data were obtained by spiking blank samples at three concentration levels (10, 50 and 200 microg/kg) over five replicates, yielding average recoveries in the range 70-121% with a RSD evaluated between 2-15%. Linearity was fixed in the range of 10-300 microg/kg with determination coefficients (R2) superior or equal to 0.9814 for all target analytes. Best LODs and LOQs were established as 0.03 and 0.1 microg/kg, respectively. Total instrumental analysis of all molecules was carried out in less than 1 h.

The biofilm electrode sensor (BFE) is designed for the rapid and sensitive detection of toxic and pathogenic environmental contaminants and industrial effluents. It includes a dissolved oxygen electrode which senses respiration changes induced in a biomass film. This study assessed the effects of five chemical on biofilms of Saccharomyces cerevisiae, and polio virus on biofilms of Buffalo Green Monkey kidney cells (BGMk). Acute toxicity was assessed in 30 min, and viral infectivity in 15-20 hr. Potassium cyanide and cupric nitrate inhibited respiration in a similar manner, 2.5-68.2 %I and 30.2-68.8 %I, respectively. The response of the BFE to cyanide and cupric ions occurred within 5-20 sec. Cadmium ions affected the BFE over the range of 50.0-1000 mg/l, but complexed with components in the support medium at lower concentrations. 2,4-dinitrophenol enhanced respiration in the concentration range of 10.0-50.0 mg/l and inhibited respiration in the concentration range of 85.0-100.0 mg/l. A maximum response of 19 %I was noted at 1200 mg/l phenol, before dissolution of the polysulfone membrane filter occurred. Detection of viruses utilized BGMk cells exposed to 4.7 {times} 10{sup 4}{minus}4.7 {times} 10{sup 8} ID{sub 50}/ml poliovirus for 2 hr prior to immobilization. The response of the BFE was optimal at 15-20 hr, with a %I range of 5-40%.

The use of nanoparticles (NPs) offers exciting new options in technical and medical applications provided they do not cause adverse cellular effects. Cellular effects of NPs depend on particle parameters and exposure conditions. In this study, whole genome expression arrays were employed to identify the influence of particle size, cytotoxicity, protein coating, and surface functionalization of polystyrene particles as model particles and for short carbon nanotubes (CNTs) as particles with potential interest in medical treatment. Another aim of the study was to find out whether screening by microarray would identify other or additional targets than commonly used cell-based assays for NP action. Whole genome expression analysis and assays for cell viability, interleukin secretion, oxidative stress, and apoptosis were employed. Similar to conventional assays, microarray data identified inflammation, oxidative stress, and apoptosis as affected by NP treatment. Application of lower particle doses and presence of protein decreased the total number of regulated genes but did not markedly influence the top regulated genes. Cellular effects of CNTs were small; only carboxyl-functionalized single-walled CNTs caused appreciable regulation of genes. It can be concluded that regulated functions correlated well with results in cell-based assays. Presence of protein mitigated cytotoxicity but did not cause a different pattern of regulated processes. - Highlights: • Regulated functions were screened using whole genome expression assays. • Polystyrene particles regulated more genes than short carbon nanotubes. • Protein coating of polystyrene particles did not change regulation pattern. • Functions regulated by microarray were confirmed by cell-based assay.

Life Cycle Impact Assessment (LCIA) and Risk Assessment (RA) employ different approaches to evaluate toxic impact potential for their own general applications. LCIA is often used to evaluate toxicity potentials for corporate environmental management and RA is often used to evaluate a risk score for environmental policy in government. This study evaluates the cancer, non-cancer, and ecotoxicity potentials and risk scores of chemicals and industry sectors in the United States on the basis of the LCIA- and RA-based tools developed by U.S. EPA, and compares the priority screening of toxic chemicals and industry sectors identified with each method to examine whether the LCIA- and RA-based results lead to the same prioritization schemes. The Tool for the Reduction and Assessment of Chemical and other environmental Impacts (TRACI) is applied as an LCIA-based screening approach with a focus on air and water emissions, and the Risk-Screening Environmental Indicator (RSEI) is applied in equivalent fashion as an RA-based screening approach. The U.S. Toxic Release Inventory is used as the dataset for this analysis, because of its general applicability to a comprehensive list of chemical substances and industry sectors. Overall, the TRACI and RSEI results do not agree with each other in part due to the unavailability of characterization factors and toxic scores for select substances, but primarily because of their different evaluation approaches. Therefore, TRACI and RSEI should be used together both to support a more comprehensive and robust approach to screening of chemicals for environmental management and policy and to highlight substances that are found to be of concern from both perspectives.

Little information is available regarding the potential for many commercial chemicals to induce developmental toxicity. The mESC Adherent Cell Differentiation and Cytoxicity (ACDC) assay is a high-throughput screen used to close this data gap. Thus, ToxCast™ Phase I chemicals wer...

Assessing the potential health risks of environmental chemical compounds is an expensive undertaking which has motivated the development of new alternatives to traditional in vivo toxicological testing. One approach is to stage the evaluation, beginning with less expensive and higher throughput in vitro testing before progressing to more definitive trials. In vitro testing can be used to generate a hypothesis about a compound's mechanism of action, which can then be used to design an appropriate in vivo experiment. Here we begin to address the question of how to design such a battery of in vitro cell-based assays by combining data from two different types of assays, cell viability and caspase activation, with the aim of elucidating mechanism of action. Because caspase activation is a transient event during apoptosis, it is not possible to design a single end-point assay protocol that would identify all instances of compound-induced caspase activation. Nevertheless, useful information about compound mechanism of action can be obtained from these assays in combination with cell viability data. Unsupervised clustering in combination with Dunn's cluster validity index is a robust method for identifying mechanisms of action without requiring any a priori knowledge about mechanisms of toxicity. The performance of this clustering method is evaluated by comparing the clustering results against literature annotations of compound mechanisms. PMID:18281954

This study aimed to evaluate the potential toxicity and safety of ethyl hydrogen adipate (EHA) by determining its effect on the reproductive function and development of Sprague-Dawley (SD) rats at dose levels of 0 (control), 200, 400, and 800 mg/kg/day. One male and five females of the 800 mg/kg/day died. Body weight loss was observed in the males of the 800 mg/kg/day and in females of the 400 and 800 mg/kg/day. In addition, mating indices decreased and pre-implantation loss rates increased in parental animals of the 400 and 800 mg/kg/day. The gestation index decreased in the male and female rats of the 800 mg/kg/day. Moreover, the body weight of the pups from the 800 mg/kg/day group decreased on post-parturition day 4. These results indicated that the no-observed-adverse-effect level of EHA for parental males and females was 400 mg/kg/day and 200 mg/kg/day, respectively, and that for pups was 400 mg/kg/day. PMID:27818735

A large monitoring study of freshwater sediments, using the TRIAD approach, was conducted in Flanders (Belgium). This paper reports on the results of the toxicity assessment of 80 sediment samples evaluated with a battery of microbiotests and conventional assays. Sediment pore waters, extracted by squeezing, were tested with the Microtox{reg_sign} (Vibrio fischerii) and Thamnotoxkit{trademark} F (Thamnocephalus platyurus) microbiotests and the conventional (acute) assays with algae (Selenastrum capricornutum) and daphnids (Daphnia magna). A newly developed 5 day ELS test with the catfish Clarias gariepinus was also applied to the pore waters. Solid-phase testing was performed with the Microtox Sp{reg_sign} assay and the 10 day tests with Chironomus riparius and Hyalella azteca. Uni- and multivariate statistical techniques were applied to the data matrix to select a minimal test battery from the water phase and solid phase assays and from all tests combined. The influence of sediment associated confounding factors on the validity of the test results obtained with the various assays will be discussed. Finally a comparison of the predictive power of the selected battery of signal tests and that of the complete battery will be made and the potential use of the minimal battery for the initial hazard assessment of contaminated sediments will be reviewed.

This report contains an update through June 2016 of the results of routinescreening for antibodies to the human immunodeficiency virus (HIV) among civilian applicants for military service and among members of the active and reserve components of the U.S. Armed Forces. During the surveillance period, annual seroprevalences among civilian applicants for military service peaked in 2015 (0.31 per 1,000 tested), up 29% from 2014 (0.24 per 1,000 tested). Seroprevalences among Marine Corps reservists, Navy active component service members, and Navy reservists also peaked in 2015. In the Army National Guard and the reserve component of the Marine Corps, full-year seroprevalences have trended upward since 2011. Overall (January 2011-June 2016) seroprevalences were highest for Army reservists, Army National Guard members, Navy active component members, and Navy reservists. Among active and reserve component service members, seroprevalences continue to be higher among Army and Navy members and males than their respective counterparts.

Tree core samples have been used to delineate organic subsurface plumes. In 2009 and 2010, samples were taken at trees growing on a former dump site in Norway and analyzed for arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), and zinc (Zn). Concentrations in wood were in averages (dw) 30 mg/kg for Zn, 2 mg/kg for Cu, and < 1 mg/kg for Cd, Cr, As and Ni. The concentrations in wood samples from the polluted test site were compared to those derived from a reference site. For all except one case, mean concentrations from the test site were higher than those from the reference site, but the difference was small and not always significant. Differences between tree species were usually higher than differences between reference and test site. Furthermore, all these elements occur naturally, and Cu, Ni, and Zn are essential minerals. Thus, all trees will have a natural background of these elements, and the occurrence alone does not indicate soil pollution. For the interpretation of the results, a comparison to wood samples from an unpolluted reference site with same species and similar soil conditions is required. This makes the tree core screening method less reliable for heavy metals than, e.g., for chlorinated solvents.

A prospective multicenter cohort study comprising 1,171 individuals who were seropositive for human immunodeficiency virus (HIV) but did not have AIDS at the time of enrollment and 182 HIV-seronegative controls, was studied by means of routine induced-sputum analysis in an attempt to detect occult tuberculosis or Pneumocystis carinii pneumonia. One occult case of tuberculosis was discovered upon the patient's enrollment (at baseline); none were discovered during follow-up. Two additional Mycobacterium tuberculosis isolates were recovered (one at baseline, one during follow-up) from subjects with symptoms or abnormalities evident on chest roentgenograms. Three specimens were false-positive (one for M. tuberculosis, two for P. carinii). Five pathogenic nontuberculous mycobacteria isolates were recovered during follow-up. Nonpathogenic, nontuberculous mycobacteria were recovered from 51 (4.6%) of 1,113 baseline specimens and 56 (3.7%) of 1,518 follow-up specimens, primarily at a center where the water supply was contaminated. We conclude that routine induced-sputum analysis is not an effective strategy for screening HIV-infected asymptomatic subjects for tuberculosis or P. carinii pneumonia before the onset of clinically recognizable disease activity.

M5 fiber is a high-strength, high-performance organic fiber type that is a rigid rod material and composed of heterocyclic polymer fibers of type PIPD. The aim of this study was to evaluate the acute lung toxicity of intratracheally instilled M5 respirable fibers and particulates in rats. Using a pulmonary bioassay and bridging methodology, the acute lung toxicity of intratracheally instilled M5 particulates and that of its fibers were compared with a positive control particle type, quartz, as well as a negative control particle type, carbonyl iron particles. Moreover, the results of these instillation studies were bridged with data previously generated from inhalation studies with quartz and carbonyl iron particles, using the quartz and iron particles as the inhalation/instillation bridge material. For the bioassay experimental design, in the bronchoalveolar lavage studies, the lungs of rats were intratracheally instilled with 0.5 or 0.75 mg/kg of M5 particulate or 1 or 5 mg/kg of the following control or particle types: (1) M5 long fiber preparation, (2) silica-quartz particles, and (3) carbonyl iron particles. Phosphate-buffered saline (PBS)-instilled rats served as additional controls. Following exposures, the lungs of PBS and particle-exposed rats were assessed using bronchoalveolar lavage (BAL) fluid biomarkers, cell proliferation methods, and histopathological evaluation of lung tissue at 24 h, 1 wk, 1 mo and 3 mo post instillation exposure. The bronchoalveolar lavage results demonstrated that lung exposures to quartz particles, at both concentrations but particularly at the higher dose, produced significant increases vs. controls in pulmonary inflammation and cytotoxicity indices. Exposures to M5 particulate and M5 long fiber preparation produced transient inflammatory and cell injury effects at 24 h postexposure (pe) as well as at 24 h and 1 wk pe, respectively, but these effects were not sustained when compared to quartz-silica effects. Exposures to

Sediment toxicity tests were conducted in the Duluth-Superior Harbor at 40 sites as part of an integrated sediment assessment during the fall of 1993. Two rapid assays conducted with Photobacterium phosphoreum (Microtox{reg_sign} and Mutatox{reg_sign}) were compared with three standard US EPA sediment toxicity tests: Hyalella azteca (acute tests) and Chironomus tentans (acute and sub-lethal tests). The response in the two microbial assays was also evaluated for sensitivity to various contaminants analyzed simultaneously in the Duluth-Superior Harbor sediments. Microtox{reg_sign} and Mutatox{reg_sign} were found to be sensitive to approximately one-third and one-half the sediments, respectively; Chironomus tentans was sensitive to 15% of the sediments (either acutely or sub-lethally), while Hyalella azteca was not sensitive to any of the sediments. In almost all cases, Microtox{reg_sign} and Mutatox{reg_sign} correctly identified samples that were toxic to the chironomid, making it useful as a screening tool for toxicity, to reduce the number of sites to be tested with the benthic organisms. The subsequent application of Microtox{reg_sign} as a screen for sediment toxicity in an EMAP survey in the St. Louis River (MN) estuary will be discussed. Correlation of Microtox{reg_sign} and Mutatox{reg_sign} toxicity to environmental contaminants found in the sediments will be presented.

The accumulation of amyloid β peptide (Aβ) in the brain of Alzheimer’s disease (AD) patients begins many years before clinical onset. Such process has been proposed to be pathogenic through the toxicity of Aβ soluble oligomers leading to synaptic dysfunction, phospho-tau aggregation and neuronal loss. Yet, a massive accumulation of Aβ can be found in approximately 30% of aged individuals with preserved cognitive function. Therefore, within the frame of the “amyloid hypothesis”, compensatory mechanisms and/or additional neurotoxic or protective factors need to be considered and investigated. Here we describe a modifier genetic screen in Drosophila designed to identify genes that modulate toxicity of Aβ42 in the CNS. The expression of Aβ42 led to its accumulation in the brain and a moderate impairment of negative geotaxis at 18 days post-eclosion (d.p.e) as compared with genetic or parental controls. These flies were mated with a collection of lines carrying chromosomal deletions and negative geotaxis was assessed at 5 and 18 d.p.e. Our screen is the first to take into account all of the following features, relevant to sporadic AD: (1) pan-neuronal expression of wild-type Aβ42; (2) a quantifiable complex behavior; (3) Aβ neurotoxicity associated with progressive accumulation of the peptide; and (4) improvement or worsening of climbing ability only evident in aged animals. One hundred and ninety-nine deficiency (Df) lines accounting for ~6300 genes were analyzed. Six lines, including the deletion of 52 Drosophila genes with human orthologs, significantly modified Aβ42 neurotoxicity in 18-day-old flies. So far, we have validated CG11796 and identified CG17249 as a strong candidate (whose human orthologs are HPD and PRCC, respectively) by using RNAi or mutant hemizygous lines. PRCC encodes proline-rich protein PRCC (ppPRCC) of unknown function associated with papillary renal cell carcinoma. HPD encodes 4-hydroxyphenylpyruvate dioxygenase (HPPD), a key

Alternative methods, replacing animal testing, are urgently needed in view of the European regulatory changes in the field of cosmetic products and their ingredients. In this context, a joint research initiative called SEURAT was recently raised by the European Commission and COLIPA, representing the European cosmetics industry, with the overall goal of developing an animal-free repeated dose toxicity testing strategy for human safety assessment purposes. Although cosmetic ingredients are usually harmless for the consumer, one of the initial tasks of this research consortium included the identification of organs that could potentially be affected by cosmetic ingredients upon systemic exposure. The strategy that was followed hereof is described in the present paper and relies on the systematic evaluation, by using a self-generated electronic databank, of published reports issued by the scientific committee of DG SANCO responsible for the safety of cosmetic ingredients. By screening of the repeated dose toxicity studies present in these reports, it was found that the liver is potentially the most frequently targeted organ by cosmetic ingredients when orally administered to experimental animals, followed by the kidney and the spleen. Combined listing of altered morphological, histopathological, and biochemical parameters subsequently indicated the possible occurrence of hepatotoxicity, including steatosis and cholestasis, triggered by a limited number of cosmetic compounds. These findings are not only of relevance for the in vitro modeling efforts and choice of compounds to be tested in the SEURAT project cluster, but also demonstrate the importance of using previously generated toxicological data through an electronic databank for addressing specific questions regarding the safety evaluation of cosmetic ingredients.

The presence of a reproductive toxicant in drinking water is one possible explanation of differences in spontaneous abortion rates between women who drink tapwater and those who do not. As part of the investigation conducted by the California Department of Health Services, several routine water quality assays were used to screen water sources available to the populations studied. I reviewed information in the literature about the potential reproductive toxicity of contaminants detected in these assays. None of these contaminants was clearly linked to increased incidence of abortion in the studies reviewed.56 references.

The study was done to assess the phytochemicals (flavonoids, terpenoids, saponins, tannin, alkaloids, and phenol) in different parts (root, stem, and leaves) of Ballota nigra and correlated it to inhibition of microbes (bacteria and fungi), protozoan (Leishmania), and heavy metals toxicity evaluation. In root and stem flavonoids, terpenes and phenols were present in ethanol, chloroform, and ethyl acetate soluble fraction; these were found to be the most active inhibiting fractions against all the tested strains of bacteria, fungi, and leishmania. While in leaves flavonoids, terpenes, and phenols were present in ethanol, chloroform, and n-butanol fractions which were the most active fractions against both types of microbes and protozoan (leishmania) in in vitro study. Ethanol and chloroform fractions show maximum inhibition against Escherichia coli (17 mm). The phytochemical and biological screenings were correlated with the presence of heavy metals in selected plant Ballota nigra. Cr was found above permissible value (above 1.5 mg/kg) in all parts of the plant. Ni was above WHO limit in B. nigra root and leaves (3.35 ± 1.20 mg/kg and 5.09 ± 0.47 mg/kg, respectively). Fe was above permissible value in all parts of B. nigra (above 20 mg/kg). Cd was above permissible value in all parts of the plant (above 0.3 mg/kg). Pb was above WHO limit (above 2 mg/kg) in all parts of Ballota nigra.

Using PCR,257 isolates of Bacillus thuringiensis(Bt) were screened for cry-type genes. Of 257 isolates/strains, 60 isolates were identified as cry7/8, 10 isolates as cry3 and 36 isolates as cry 1I. One specific strain of B. thuringiensis (sumiyoshiensis; T03B 001) was investigated for the presence of cry7 and cry8 genes. Genes Cry7 and cry8 were first detected in this strain using family primers prior to analysis by exclusion polymerase chain reaction (E-PCR) using specific type primers. E-PCR conducted with the above said primers led to the identification by agarose gel electrophoresis of a remaining 1.5 Kb family band indicating a potentially novel gene. This PCR product, (1.5 Kb), was purified from the gel and cloned in pGEM-T Easy vector. Twenty recombinant colonies bearing 1.5 Kb insert were identified and three randomly selected representatives of the group, clones 7, 8 and 10, were sequenced and compared to all cry7 and cry8 sequences available from Gene Bank. Alignments with available DNA and protein sequences showed that all these clones contained a gene related to cry8Aa1. Analysis using protein sequence alignment showed that the sequence from clone 7 differed from the closest relative, known under the new nomenclature as cry 8Aa1, by 44%. The crystal proteins from B. thuringiensis sumiyoshiensis (T03B 001) was toxic to coffee berry borer larvae.

Cigarette smoke is a complex mixture consisting of more than 5600 identified chemical constituents of which approximately 150 have been identified so far as "tobacco smoke toxicants". Proposals made by the World Health Organisation Framework Convention on Tobacco Control mandate the lowering of nine tobacco smoke priority toxicants, including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosonornicotine (NNN), and benzo[a]pyrene (B[a]P) and monitoring the levels of a further nine including cadmium. Here, we evaluated the genotoxic potential in human bronchial epithelial BEAS-2B cells of four cigarette smoke toxicants; NNK, NNN, B[a]P and cadmium using the novel in vitro γH2AX assay by High Content Screening (HCS). We also examined the genotoxicity of binary mixtures of NNK and NNN reporting their relative contribution to the genotoxic end-point. The results of this preliminary assessment showed that the in vitro γH2AX assay by HCS could be used as a pre-screening tool to detect and quantify the genotoxicity effect of cigarette smoke toxicants individually and in binary mixture. Moreover, the data produced could contribute to the prioritisation of toxicant reduction research in modified tobacco products.

included the deposition of smoke screen constituents onto vegetation and soil fol- lowed by procipitation and runoff into a body of water. The research...lumens mŖ). Charcoal filtered aeration was provided to enhance growth. Algae were grown in EPA media (Miller, Greene and Shiroyama 1978) for toxicity...the water could affect the potential for acidification. Prolonged contact with soil or suspended dust may accelerate the decomposition of the more

Testing of environmental and industrial chemicals for toxicity potential is a daunting task because of the wide range of possible toxicity mechanisms. Although animal testing is one means of achieving broad toxicity coverage, evaluation of large numbers of chemicals is challengin...

What is a routine question? The focus of this paper is routine questions and time (in years) since a hitherto routine question was last attempted by the solver. The data comes from undergraduate students' work on solving two calculus questions. The data was selected for reporting purposes because it is well documented and because it threw up…

Microband biosensors, screen-printed from a water-based carbon ink containing cobalt phthalocyanine redox mediator and glucose oxidase (GOD) enzyme, were used to monitor glucose levels continuously in buffer and culture medium. Five biosensors were operated amperometrically (E(app) of +0.4V), in a 12-well tissue culture plate system at 37°C, using a multipotentiostat. After 24 h, a linear calibration plot was obtained from steady-state current responses for glucose concentrations up to 10 mM (dynamic range 30 mM). Within the linear region, a correlation coefficient (R(2)) of 0.981 was obtained between biosensor and spectrophotometric assays. Over 24 h, an estimated 0.15% (89 nmol) of the starting glucose concentration (24 mM) was consumed by the microbiosensor. The sensitivity of the biosensor response in full culture medium was stable between pHs 7.3 and 8.4. Amperometric responses for HepG2 monolayer cultures decreased with time in inverse proportionality to cell number (for 0 to 10(6) cell/ml), as glucose was being metabolised. HepG2 3D cultures (spheroids) were also shown to metabolise glucose, at a rate which was independent of spheroid age (between 6 and 15 days). Spheroids were used to assay the effect of a typical hepatotoxin, paracetamol. At 1 mM paracetamol, glucose uptake was inhibited by 95% after 6 h in culture; at 500 μM, around 15% inhibition was observed after 16 h. This microband biosensor culture system could form the basis for an in vitro toxicity testing system.

This report contains an update through June 2014 of the results of routinescreening for antibodies to the human immunodeficiency virus (HIV) among civilian applicants for military service and among members of the active and reserve components of the U.S. Armed Forces. Seroprevalences among civilian applicants in 2013 and the first half of 2014 (0.19 and 0.15 per 1,000 tested, respectively) were markedly lower than in 2012 (0.27 per 1,000 tested). In nearly every component of every service, seroprevalences in 2013 and 2014 were either similar or lower than in prior years; however, in the Army National Guard, seroprevalences increased each year and approximately doubled from 2010 (0.18 per 1,000 tested) to 2013-2014 (0.35-0.41 per 1,000 tested). Among active and reserve component service members, seroprevalences continue to be higher among Army and Navy members and males than their respective counterparts.

This report contains an update through June 2015 of the results of routinescreening for antibodies to the human immunodeficiency virus (HIV) among civilian applicants for military service and among members of the active and reserve components of the U.S. Armed Forces. Seroprevalences among civilian applicants in 2014 and the first half of 2015 (0.21 and 0.22 per 1,000 tested, respectively) were markedly lower than in 2012 (0.28 per 1,000 tested). In nearly every component of every military service, seroprevalences in 2014 and 2015 were either lower than, or relatively similar to, prevalences in prior years; however, in the Army National Guard, seroprevalences increased each year and approximately doubled from 2010 (0.18 per 1,000 tested) to 2014-2015 (0.36-0.39 per 1,000 tested). Among active and reserve component service members, seroprevalences continue to be higher among Army and Navy members and males than their respective counterparts.

Surrounded by landfills, and toxic and hazardous facilities, Altgeld Gardens is located in a “toxic doughnut.” With high rates of environmentally-related conditions, residents have called for a community-based environmental health assessment to improve overall health in their com...

The risk factors associated with the use of glucose-6-phosphate dehydrogenase (G6PD)-deficient blood in transfusion have not yet been well established. Therefore, the aim of this review was to evaluate whether whole blood from healthy G6PD-deficient donors is safe to use for transfusion. The study undertook a systematic review of English articles indexed in COCHRANE, MEDLINE, EMBASE, and CINHAL, with no date restriction up to March 2013, as well as those included in articles' reference lists and those included in Google Scholar. Inclusion criteria required that studies be randomized controlled trials, case controls, case reports, or prospective clinical series. Data were extracted following the Preferred Reporting Items for Systematic Reviews using a previously piloted form, which included fields for study design, population under study, sample size, study results, limitations, conclusions, and recommendations. The initial search identified 663 potentially relevant articles, of which only 13 studies met the inclusion criteria. The reported effects of G6PD-deficient transfused blood on neonates and children appear to be more deleterious than effects reported on adult patients. In most cases, the rise of total serum bilirubin was abnormal in infants transfused with G6PD-deficient blood from 6 hours up to 60 hours after transfusion. All studies on neonates and children, except one, recommended a routinescreening for G6PD deficiency for this at-risk subpopulation because their immature hepatic function potentially makes them less able to handle any excess bilirubin load. It is difficult to make firm clinical conclusions and recommendations given the equivocal results, the lack of standardized evaluation methods to categorize red blood cell units as G6PD deficient (some of which are questionable), and the limited methodological quality and low quality of evidence. Notwithstanding these limitations, based on our review of the available literature, there is little to

Lanestosa is a chronically polluted site (derelict mine) where the soil (Lanestosa (LA) soil) exceeds screening values (SVs) of regulatory policies in force (Basque Country; Europe) for Zn, Pb and Cd. A scenario-targeted toxicity assessment was carried out on the basis of a multi-endpoint bioassay approach. Acute and chronic toxicity bioassays were conducted with selected test species (Vibrio fischeri, Dictyostelium discoideum, Lactuca sativa, Raphanus sativus and Eisenia fetida) in combination with chemical analysis of soils and elutriates and with bioaccumulation studies in earthworms. Besides, the toxicity profile was compared with that of the mine runoff (RO) soil and of a fresh artificially polluted soil (LAAPS) resembling LA soil pollutant profile. Extractability studies in LA soil revealed that Pb, Zn and Cd were highly available for exchange and/or release into the environment. Indeed, Pb and Zn were accumulated in earthworms and LA soil resulted to be toxic. Soil respiration, V. fischeri, vegetative and developmental cycles of D. discoideum and survival and juvenile production of E. fetida were severely affected. These results confirmed that LA soil had unacceptable environmental risk and demanded intervention. In contrast, although Pb and Zn concentrations in RO soil revealed also unacceptable risk, both metal extractability and toxicity were much lower than in LA soil. Thus, within the polluted site, the need for intervention varied between areas that posed dissimilar risk. Besides, since LAAPS, with a high exchangeable metal fraction, was the most toxic, ageing under in situ natural conditions seemingly contributed to attenuate LA soil risk. As a whole, combining multi-endpoint bioassays with scenario-targeted analysis (including leaching and ageing) provides reliable risk assessment in soils posing unacceptable environmental risk according to SVs, which is useful to optimise the required intervention measures.

To anticipate to increased testing needs for reproductive toxicity and 3R approaches, we studied zebrafish embryo/larva as an alternative for animal testing for developmental toxicity and embryotoxicity and evaluated a training set of 27 compounds with a standardized protocol. The classification of compounds in the zebrafish embryo/larva assay, based on a prediction model using a TI (teratogenic index) cut-off value of 2, was compared to available animal and human data. When comparing the classification of compounds in the zebrafish embryo/larva assay to available animal classification, a sensitivity of 72% and specificity of 100% were obtained. The predictive values obtained in comparison to a limited set of human data were 50, 60% respectively for teratogens, non-teratogens. Overall, we demonstrated that the zebrafish embryo/larva assay, may be used as screening tool for prioritization of compounds and could contribute to reduction of animal experiments in the field of developmental toxicology.

There is a growing demand for in vitro assays for toxicityscreening in three-dimensional (3D) environments. In this study, 3D cell culture using magnetic levitation was used to create an assay in which cells were patterned into 3D rings that close over time. The rate of closure was determined from time-lapse images taken with a mobile device and related to drug concentration. Rings of human embryonic kidney cells (HEK293) and tracheal smooth muscle cells (SMCs) were tested with ibuprofen and sodium dodecyl sulfate (SDS). Ring closure correlated with the viability and migration of cells in two dimensions (2D). Images taken using a mobile device were similar in analysis to images taken with a microscope. Ring closure may serve as a promising label-free and quantitative assay for high-throughput in vivo toxicity in 3D cultures.

High-throughput in vitro screening and computational tools provide government an efficient way to identify those chemicals that warrant further testing while conserving limited testing resources. Incorporation of kinetic and exposure information should provide a more meaningful i...

... page: //medlineplus.gov/ency/patientinstructions/000891.htm Outdoor fitness routine To use the sharing features on this ... you and is right for your level of fitness. Here are some ideas: Warm up first. Get ...

Dictyostelium discoideum is a single-cell, eukaryotic microorganism that can undergo multicellular development in order to produce dormant spores. We investigated the capacity of D. discoideum to be used as a rapid screening system for potential developmental toxicity of compounds under development as pharmaceuticals. We used a set of four transgenic D. discoideum strains that expressed a reporter gene under the control of promoters that are active at certain time periods and in distinct cell types during D. discoideum development. We found that teratogens such as valproic acid, tretinoin, or thalidomide interfered to various extents with D. discoideum development, and had different effects on prestalk and prespore cell-specific reporter gene expression. Phenytoin was inactive in this assay, which may point to limitations in metabolization of the compound in Dictyostelium required to exert developmental toxicity. D. discoideum cell culture is cheap and easy to handle compared to mammalian cell cultures or animal teratogenicity models. Although the Dictyostelium-based assay described in this report may not securely predict the teratogenic potential of these drugs in humans, this organism may be qualified for rapid large-scale screenings of synthetic compounds under development as new pharmaceuticals for their potential to interfere with developmental processes and thus help to reduce the amount of teratogenicity tests in animal models.

Alpha-Synuclein (aSyn) misfolding and aggregation is common in several neurodegenerative diseases, including Parkinson’s disease and dementia with Lewy bodies, which are known as synucleinopathies. Accumulating evidence suggests that secretion and cell-to-cell trafficking of pathological forms of aSyn may explain the typical patterns of disease progression. However, the molecular mechanisms controlling aSyn aggregation and spreading of pathology are still elusive. In order to obtain unbiased information about the molecular regulators of aSyn oligomerization, we performed a microscopy-based large-scale RNAi screen in living cells. Interestingly, we identified nine Rab GTPase and kinase genes that modulated aSyn aggregation, toxicity and levels. From those, Rab8b, Rab11a, Rab13 and Slp5 were able to promote the clearance of aSyn inclusions and rescue aSyn induced toxicity. Furthermore, we found that endocytic recycling and secretion of aSyn was enhanced upon Rab11a and Rab13 expression in cells accumulating aSyn inclusions. Overall, our study resulted in the identification of new molecular players involved in the aggregation, toxicity, and secretion of aSyn, opening novel avenues for our understanding of the molecular basis of synucleinopathies. PMID:27123591

Eight whole sediment samples from Antarctica (four from Winter Quarters Bay and four from McMurdo Sound) were toxicologically and chemically evaluated. Also, the influence of ultraviolet radiation on the toxicity and bioavailability of contaminants associated with the sediment samples was assessed. The evaluations were accomplished by use of a 10-day whole sediment test with Leptocheirus plumulosus, Microtox®, Mutatox® and semipermeable membrane devices (SPMDs). Winter Quarters Bay sediments contained about 250 ng g−1 (dry weight) total PCBs and 20 μg g−1 total PAHs. These sediments elicited toxicity in the Microtox test and avoidance and inhibited burrowing in the L. plumulosus test. The McMurdo Sound sediment samples contained only trace amounts of PCBs and no PAHs, and were less toxic in both the L. plumulosus and Microtox tests compared to the Winter Quarters Bay sediments. The sediments from McMurdo Sound apparently contained some unidentified substance which was photolytically modified to a more toxic form. The photolytic modification of sediment-associated contaminants, coupled with the polar ozone hole and increased incidence of ultraviolet radiation could significantly increase hazards to Antarctic marine life.

New toxicity testing approaches will rely on in vitro assays to assess chemical effects at the cellular and molecular level. Cell proliferation is imperative to normal development, and chemical disruption of this process can be detrimental to the organism. As part of an effort to...

Techniques for the field characterization of soil contamination due to spillage of hazardous waste or toxic chemicals are time-consuming and expensive. Thus, more economical, less time-intensive methods are needed to facilitate rapid field screening of contaminated sites. In situ detection of toxic chemicals in soil offers both time and cost advantages for field screening with additional application to real-time site monitoring. Fourier-transform infrared (FT-IR) spectroscopy coupled with evanescent mode fiber-optic sensors has been demonstrated as a means to remotely detect and classify petroleum products in water using mid-infrared (MIR) optical fibers. This work demonstrated that a fiber-optic evanescent field absorbance sensor (EFAS) could be used to classify petroleum contamination into categories such as crude oil, kerosene, No. 2 fuel and residual distillates using the MIR spectral range. The overall objective of this project is to study the feasibility of using an EFAS FT-IR spectroscopic sensor coupled with cone penetrometry as a field screening method. The Fourier transform infrared cone penetrometry method (FT-IR-CPT) will be developed by building on the work cited above. The specific objectives of this project are: design an accessory for use with FT-IR that interfaces the spectrometer to a cone penetrometer; characterize the response of the FT-IR accessory to selected hydrocarbons in a laboratory-simulated field environment; and determine the ability of the FT-IR-CPT instrument to measure hydrocarbon contamination in soil by direct comparison with a reference method to quantify hydrocarbons from the same soil.

Car tires contain several water-soluble compounds that can leach into water and have toxic effects on aquatic organisms. Due to tire wear, 10,000 tonnes of rubber particles end up along the Swedish roads every year. This leads to a diffuse input of emissions of several compounds. Emissions of polyaromatic hydrocarbons (PAHs) are of particular concern. PAHs are ingredients of the high aromatic oil (HA oil) that is used in the rubber as a softener and as a filler. The exclusion of HA oils from car tires has started, and an environmental labeling of tires could make HA oils obsolete. The toxicity to Daphnia magna from 12 randomly selected car tires was tested in this study. Rubber from the tread of the tires was grated into small pieces, to simulate material from tire wear, and the rubber was equilibrated with dilution water for 72 h before addition of test organisms. The 24-h EC50s of the rubber pieces ranged from 0.29 to 32 gl-1, and the 48-h EC50s ranged from 0.0625 to 2.41 gl-1. Summer tires were more toxic than winter tires. After the 48-h exposure, the daphnids were exposed to UV-light for 2 h, to determine if the tires contained compounds that were phototoxic. After UV-activation the EC50s ranged from 0.0625 to 0.38 gl-1. Four of the 12 tires had a very distinct photoactivation, with a toxicity increase of >10 times. This study has shown that the used method for toxicity testing with Daphnia magna according to ISO 6341 could be used as a basis for environmental labeling of car tires.

Ports and harbors may represent a threat for coastal ecosystems due to pollutant inputs, especially those derived from maritime activities. In this study, we report a first assessment of the ecotoxicological threat posed by six ports and harbors of opposite coastal regions, Apulia and Albania, in the southern Adriatic Sea (Italy). A bioassay battery consisting of four different species representing different trophic levels, algae Dunaliella tertiolecta, bacteria Vibrio fischeri, crustacean Artemia salina, and echinoids Paracentrotus lividus, has been used to assess sediment elutriates, pore waters, and sediment suspensions. Two different approaches of toxicity data integration, worst case and integrated index, have been used to determine the most appropriate procedure for the investigated sites. All sites with the worst case approach showed high toxicity levels. The chronic test with algae was the most sensitive identifying the highest effects in the battery. This effect can be attributable to contaminants derived from antifouling paints. The sediments, evaluated with V. fischeri test, often showed toxicity not found in the aqueous matrices of the same sites and that can be mainly linked to organic compounds. The test battery used in this study allowed us to perform a preliminary screening of the ecotoxicological risk of the studied area. In fact, the species utilized for toxicity tests responded differently to the investigated samples, showing different sensitivity. The test battery integrated index did not allow highlighting the differences among the sites and showed a general high ecotoxicological risk. A larger number of tests with higher sensitivity together with a tailored attribution of weights to endpoints and matrices will improve the final site evaluation.

The guide describes some of the challenges raised by the Toxic Release Inventory (TRI) data and to suggest ways of approaching them. The guide suggests steps that can be taken to answer two key issues of concern: setting risk-based priorities for followup investigation of the TRI facilities and chemicals within geographic area of interest, and identifying data needs and approaches for collecting information necessary to respond to health and ecological questions from the public. The guide is directed at those individuals who are involved in interpreting and explaining environmental pollution, exposures, and health risks to the general public, especially at the local or sub-State level. Many users of the guide will already be well versed in evaluating risk and/or in helping members of the public understand and deal with toxic chemicals, but Title 111 - particularly, the Section 313 release data - presents new challenges for everyone.

Efficient protocols to differentiate human pluripotent stem cells to various tissues in combination with -omics technologies opened up new horizons for in vitro toxicity testing of potential drugs. To provide a solid scientific basis for such assays, it will be important to gain quantitative information on the time course of development and on the underlying regulatory mechanisms by systems biology approaches. Two assays have therefore been tuned here for these requirements. In the UKK test system, human embryonic stem cells (hESC) (or other pluripotent cells) are left to spontaneously differentiate for 14 days in embryoid bodies, to allow generation of cells of all three germ layers. This system recapitulates key steps of early human embryonic development, and it can predict human-specific early embryonic toxicity/teratogenicity, if cells are exposed to chemicals during differentiation. The UKN1 test system is based on hESC differentiating to a population of neuroectodermal progenitor (NEP) cells for 6 days. This system recapitulates early neural development and predicts early developmental neurotoxicity and epigenetic changes triggered by chemicals. Both systems, in combination with transcriptome microarray studies, are suitable for identifying toxicity biomarkers. Moreover, they may be used in combination to generate input data for systems biology analysis. These test systems have advantages over the traditional toxicological studies requiring large amounts of animals. The test systems may contribute to a reduction of the costs for drug development and chemical safety evaluation. Their combination sheds light especially on compounds that may influence neurodevelopment specifically.

This informed commentary article offers a simple, effective classroom management strategy in which the teacher uses routine documentation to motivate students both to perform academically and to behave in a manner consistent with established classroom rules and procedures. The pragmatic strategy is grounded in literature, free to implement,…

This study provides a rare opportunity to look inside the homeschool and to observe the routines of homeschooling families from across the United States. With more than 1000 survey participants, and nine parents selected for interviews, the compiled data were analyzed through open coding techniques. Meaningful aspects that arose from the routines…

PROPER simulates the propagation of light through an optical system using Fourier transform algorithms (Fresnel, angular spectrum methods). Distributed as IDL source code, it includes routines to create complex apertures, aberrated wavefronts, and deformable mirrors. It is especially useful for the simulation of high contrast imaging telescopes (extrasolar planet imagers like TPF).

The blood-brain barrier (BBB) is a dynamic interface that maintains brain homeostasis and protects it from free entry of chemicals, toxins, and drugs. The barrier function of the BBB is maintained mainly by capillary endothelial cells that physically separate brain from blood. Several neurological diseases, such as Alzheimer's disease (AD), are known to disrupt BBB integrity. In this study, a high-throughput screening (HTS) was developed to identify drugs that rectify/protect BBB integrity from vascular amyloid toxicity associated with AD progression. Assessing Lucifer Yellow permeation across in-vitro BBB model composed from mouse brain endothelial cells (bEnd3) grown on 96-well plate inserts was used to screen 1280 compounds of Sigma LOPAC®1280 library for modulators of bEnd3 monolayer integrity. HTS identified 62 compounds as disruptors, and 50 compounds as enhancers of the endothelial barrier integrity. From these 50 enhancers, 7 FDA approved drugs were identified with EC50 values ranging from 0.76-4.56 μM. Of these 7 drugs, 5 were able to protect bEnd3-based BBB model integrity against amyloid toxicity. Furthermore, to test the translational potential to humans, the 7 drugs were tested for their ability to rectify the disruptive effect of Aβ in the human endothelial cell line hCMEC/D3. Only 3 (etodolac, granisetron, and beclomethasone) out of the 5 effective drugs in the bEnd3-based BBB model demonstrated a promising effect to protect the hCMEC/D3-based BBB model integrity. These drugs are compelling candidates for repurposing as therapeutic agents that could rectify dysfunctional BBB associated with AD.

To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicityscreening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid (VPA), carbamazepine (CBZ), ethosuximide (ETH) and levetiracetam (LEV). For VPA, histopathology was the most sensitive parameter, showing effects already at 60μM. For CBZ, morphology and MA were the most sensitive parameters, showing effects at 180μM. For ETH, all endpoints showed similar sensitivity (6.6mM), whereas MA was the most sensitive parameter for LEV (40mM). Inclusion of kinetics did not alter the absolute ranking of the compounds, but the relative potency was changed considerably. Taking all together, this demo-case study showed that inclusion of multiple-endpoints in ZET may increase the sensitivity of the assay, contribute to the elucidation of the mode of toxic action and to a better definition of the applicability domain of ZET.

In a combined repeated dose toxicity study with reproduction/developmental toxicityscreening test, Crj:CD(SD)IGS rats were dosed with dinoseb, 2-sec-butyl-4,6-dinitrophenol, by gavage at 0 (vehicle), 0.78, 2.33, or 7.0 mg/kg bw/day. Six males per group were dosed for a total of 42 days beginning 14 days before mating. Twelve females per group were dosed for a total of 44-48 days beginning 14 days before mating to day 6 of lactation throughout the mating and gestation period. Recovery groups of six males per group and nonpregnant six females per group were dosed for 42 days followed by a 14-day recovery period. No deaths were observed in males of any dose group or in females of the recovery groups. At 7.0 mg/kg bw/day, eight females died and two animals were moribund during late pregnancy, and a significant decrease in body weight gain was found in both sexes. Hematocrit was significantly higher at 0.78 mg/kg bw/day and above in the main group males at the end of administration period. Reduction in extramedullary hematopoiesis in the spleen was significant at 2.33 mg/kg bw/day in the main group females. Sperm analysis revealed a decrease in sperm motility and an increase in the rates of abnormal sperm, abnormal tail, and abnormal head at 7.0 mg/kg bw/day. A number of dams delivered their pups and of dams with live pups at delivery was significantly lowered in the 7.0 mg/kg bw/day group. Based on these findings, the LOAEL for males and NOAEL for females were 0.78 mg/kg bw/day, and the NOAEL for reproductive/developmental toxicity was considered to be 2.33 mg/kg bw/day.

As nanoparticles have found increased use in both consumer and medical applications, corresponding increases in possible exposure to humans necessitate studies examining the impacts of these nanomaterials in biological systems. This article examines the effects of approximately 30-nm-diameter gold nanoparticles, with positively and negatively charged surface coatings in human blood. Here, we study the exposure effects, with up to 72 h of exposure to 5, 15, 25 and 50 µg/ml nanoparticles on hemolysis, reactive oxygen species (ROS) generation and platelet aggregation in subsets of cells from human blood. Assessing viability with hemolysis, results show significant changes in a concentration-dependent fashion. Rates of ROS generation were investigated using the dichlorofluorscein diacetate-based assay as ROS generation is a commonly suspected mechanism of nanoparticle toxicity; herein, ROS was not a significant factor. Optical monitoring of platelet aggregation revealed that none of the examined nanoparticles induced aggregation upon short-term exposure.

Single-walled carbon nanotubes (SWCNT), fullerenes (C{sub 60}), carbon black (CB), nC{sub 60}, and quantum dots (QD) have been studied in vitro to determine their toxicity in a number of cell types. Here, we report that classical dye-based assays such as MTT and neutral red (NR) that determine cell viability produce invalid results with some NM (nanomaterials) due to NM/dye interactions and/or NM adsorption of the dye/dye products. In this study, human epidermal keratinocytes (HEK) were exposed in vitro to CB, SWCNT, C{sub 60}, nC{sub 60}, and QD to assess viability with calcein AM (CAM), Live/Dead (LD), NR, MTT, Celltiter 96 AQueous One (96 AQ), alamar Blue (aB), Celltiter-Blue (CTB), CytoTox One{sup TM} (CTO), and flow cytometry. In addition, trypan blue (TB) was quantitated by light microscopy. Assay linearity (R{sup 2} value) was determined with HEK plated at concentrations from 0 to 25,000 cells per well in 96-well plates. HEK were treated with serial dilutions of each NM for 24 h and assessed with each of the viability assays. TB, CAM and LD assays, which depend on direct staining of living and/or dead cells, were difficult to interpret due to physical interference of the NM with cells. Results of the dye-based assays varied a great deal, depending on the interactions of the dye/dye product with the carbon nanomaterials (CNM). Results show the optimal high throughput assay for use with carbon and noncarbon NM was 96 AQ. This study shows that, unlike small molecules, CNM interact with assay markers to cause variable results with classical toxicology assays and may not be suitable for assessing nanoparticle cytotoxicity. Therefore, more than one assay may be required when determining nanoparticle toxicity for risk assessment.

This document describes the Character Handling Routine library, CHR, and its use. The CHR library augments the limited character handling facilities provided by the Fortran 77 standard. It offers a range of character handling facilities: from formatting Fortran data types into text strings and the reverse, to higher level functions such as wild card matching, string sorting, paragraph reformatting and justification. The library may be used simply for building text strings for interactive applications or as a basis for more complex text processing applications.

Prediction of human response to potential therapeutic drugs is through conventional methods of in vitro cell culture assays and expensive in vivo animal testing. Alternatives to animal testing require sophisticated in vitro model systems that must replicate in vivo like function for reliable testing applications. Advancements in biomaterials have enabled the development of three-dimensional (3D) cell encapsulated hydrogels as in vitro drug screening tissue model systems. In this study, we have developed an in vitro platform to enable high density 3D culture of liver cells combined with a monolayer growth of target breast cancer cell line (MCF-7) in a static environment as a representative example of screening drug compounds for hepatotoxicity and drug efficacy. Alginate hydrogels encapsulated with serial cell densities of HepG2 cells (10{sup 5}-10{sup 8} cells/ml) are supported by a porous poly-carbonate disc platform and co-cultured with MCF-7 cells within standard cell culture plates during a 3 day study period. The clearance rates of drug transformation by HepG2 cells are measured using a coumarin based pro-drug. The platform was used to test for HepG2 cytotoxicity 50% (CT{sub 50}) using commercially available drugs which further correlated well with published in vivo LD{sub 50} values. The developed test platform allowed us to evaluate drug dose concentrations to predict hepatotoxicity and its effect on the target cells. The in vitro 3D co-culture platform provides a scalable and flexible approach to test multiple-cell types in a hybrid setting within standard cell culture plates which may open up novel 3D in vitro culture techniques to screen new chemical entity compounds. - Graphical abstract: Display Omitted Highlights: > A porous support disc design to support the culture of desired cells in 3D hydrogels. > Demonstrated the co-culture of two cell types within standard cell-culture plates. > A scalable, low cost approach to toxicityscreening involving

The world's status quo on recreational drugs has dramatically changed in recent years due to the rapid emergence of new psychoactive substances (NPS), represented by new narcotic or psychotropic drugs, in pure form or in preparation, which are not controlled by international conventions, but that may pose a public health threat comparable with that posed by substances listed in these conventions. These NPS, also known as 'legal highs' or 'smart drugs', are typically sold via Internet or 'smartshops' as legal alternatives to controlled substances, being announced as 'bath salts' and 'plant feeders' and is often sought after for consumption especially among young people. Although NPS have the biased reputation of being safe, the vast majority has hitherto not been tested and several fatal cases have been reported, namely for synthetic cathinones, with pathological patterns comparable with amphetamines. Additionally, the unprecedented speed of appearance and distribution of the NPS worldwide brings technical difficulties in the development of analytical procedures and risk assessment in real time. In this study, 27 products commercialized as 'plant feeders' were chemically characterized by gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. It was also evaluated, for the first time, the in vitro hepatotoxic effects of individual synthetic cathinones, namely methylone, pentedrone, 4-methylethcathinone (4-MEC) and 3,4-methylenedioxypyrovalerone (MDPV). Two commercial mixtures ('Bloom' and 'Blow') containing mainly cathinone derivatives were also tested, and 3,4-methylenedioxymethamphetamine (MDMA) was used as the reference drug. The study allowed the identification of 19 compounds, showing that synthetic cathinones are the main active compounds present in these products. Qualitative and quantitative variability was found in products sold with the same trade name in matching or different 'smartshops'. In the toxicity studies performed in

... data files. These routines are written in Interactive Data Language (IDL). A README file demonstrating use of the routines is also available. Interactive Data Language (IDL) is available from Exelis Visual Information Solutions . ...

Anti-cancer drugs are compounds that are of high environmental relevance because of their lack of specific mode of action. They can be extremely harmful to living organisms even at low concentrations. The present study evaluated the toxic effects of four frequently used anti-cancer drugs against plant seedlings, namely Cyclophosphamide (CP), Methotrexate (MTX), 5-Fluorouracil (5-FU) and Imatinib (IM). The phytotoxicity experiments were performed with Lactuca sativa seedlings whereas cytotoxicity, genotoxicity and mutagenicity investigations were performed with the well-established Allium cepa assays. MTX was the most phytotoxic compound, followed by 5-FU, CP and IM. Significant differences in the Mitotic Indexes (MI) were observed in three of the studied compounds (MTX, 5-FU and CP), indicating potential cytotoxic activity of these substances. Chromosome aberrations were registered in cells that were exposed to 5-FU, CP and IM. All the four compounds caused the formation of micronucleated cells indicating mutagenic potential. Besides, the assays performed with MTX samples presented a high number of cell apoptosis (cell death). Although it is unlikely that the pharmaceuticals concentrations measured in the environment could cause lethal effects in plants, the obtained results indicate that these compounds may affect the growth and normal development of these plants. So, both tests can constitute important tools for a fast screening of environmental contamination e.g. in the context of the reuse of treated wastewater and biosolids of agricultural purpose.

The major lethal factors in uncontrolled fires are toxic gases, heat, and oxygen deficiency. The predominant toxic gas is carbon monoxide, which is readily generated from the combusion of wood and other cellulosic materials. Increasing use of a variety of synthetic polymers has stimulated interest in screening tests to evaluated the toxicity of polymeric materials when thermally decomposed. As yet, this country lacks a standardized fire toxicity test protocol.

Quality management methods have been introduced into health care with variable success. Industrial approaches, such as standardization, are not always applicable professional services, because of fundamental differences in conceptions of aims and the predictability of the results of action. Processes in health care can be classified into standard, routine and non-routine depending on the level of repetition and amount of variation, variety and uncertainty. Quality problems are different in each type: standard processes may produce deviations from targets, routines errors in classification, and non-routines failures in interpretation. Different management approaches for each type are discussed. A metaphor to assist discussion, The Broom, is introduced.

During routine testing of civilian applicants for U.S. military service, the overall seroprevalence of antibodies to HIV-1 in 2011 was the second lowest of any year since 1990. Among members of the active components of the U.S. Army, HIV-1 seroprevalences were higher during 2008 to 2011 than in recent prior years. Among members of the active components of the U.S. Air Force, Navy and Marine Corps, the Marine Corps Reserve, and the Army National Guard, HIV-1 seroprevalences have slightly declined or remained relatively stable for at least ten years. In the reserve components of most service branches, it is difficult to discern long-term trends because of instability of seroprevalences in the relatively small numbers of reserve component members tested each year. Monitoring of HIV-1 seroprevalences can help target and focus prevention initiatives. The recent repeal of the Don't Ask Don't Tell policy has created opportunities for prevention messages targeted to men who have sex with men.

This report contains an update through June 2013 on the results of screening for HIV infection among civilian applicants for military service and among members of the active and reserve components of the Armed Forces. Among civilian applicants, annual rates of prevalence of HIV infection showed a continuing downward trend. Rates among black, non-Hispanic applicants were higher than other racial/ethnic groups but have declined sharply since 2008. Among service members, annual rates have varied by service and component, with higher rates in the Army and Navy and lower rates in the Marine Corps and Air Force. Members of the Army and Air Force Reserves have had consistently higher rates than members of their respective active components. For both civilian applicants and service members, rates among men are notably higher than among women. The possible roles of unprotected sex and pre-deployment behaviors and the associated challenges to prevention of HIV infection are discussed.

NATA is an ongoing comprehensive evaluation of air toxics in the U.S. As a screening tool, it helps air agencies prioritize pollutants, emission sources and locations of interest for further study to gain a better understanding of risks.

A rapid, but sensitive and selective method for simultaneous screening and quantification of toxic pyrrolizidine alkaloids (PAs) by ultra performance liquid-chromatography (UPLC) coupled with tandem mass spectrometry (MS/MS) on a tandem quadrupole mass spectrometer (TQ-MS) is described. This was accomplished by incorporating the precursor ion scan (PIS) acquisition and multiple reaction monitoring (MRM) acquisition in the same UPLC-MS/MS run. Notably, the developed PIS approach for detecting two pairs of characteristic product ions at m/z 120/138 or 168/150, allowed specific identification of toxic retronecine and otonecine types PAs. This PIS method is highly sensitive with over 10-fold sensitivity improvement upon previously published LC-MS method. Moreover, this new approach is suitable for high sample throughput and was applied to the screening and quantifying toxic PAs in 22 samples collected from seven Parasenecio species and four Senecio species. In addition, coupling the MRM with PIS approach generated quantitative results equivalent to those obtained by conventional MRM-only approach. This coupled MRM with PIS approach could provide both qualitative and quantitative results without the need of repetitive analyses.

Mitochondrial dysfunction is increasingly implicated in the etiology of drug-induced toxicities. Members of diverse drug classes undermine mitochondrial function, and among the most potent are drugs that have been withdrawn from the market, or have received Black Box warnings from the FDA. To avoid mitochondrial liabilities, routinescreens need to be positioned within the drug-development process. Assays for mitochondrial function, cell models that better report mitochondrial impairment, and new animal models that more faithfully reflect clinical manifestations of mitochondrial dysfunction are discussed in the context of how such data can reduce late stage attrition of drug candidates and can yield safer drugs in the future.

Screening for behavioral toxicity, or neurotoxicity, has been in use for decades; however, only in the past 20 years has this become a standard practice in toxicology. Current screening batteries, such as the functional observational battery (FOB), are derived from protocols use...

The toxicity of nanomaterials depends on the basic interaction of the chemistry of the material with the molecular pathways in an organism. To design safe and sustainable nanomaterials, more detailed information on the molecular interaction and biochemical machinery that is altered in an organism upon contact with a nanomaterial is needed. There are a multitude of papers now on the toxicity of nanomaterials to various model organisms from human to ecological models, but many focus on acute high dose exposures and research on the toxicity of other chemicals has shown that the dose of a chemical can have a tremendous impact on the pathways that are affected within the organism. The most common pathways investigated in nanotoxicity experiments are related to oxidative stress, yet oxidative stress can be a temporary and natural response to an insult without a negative outcome. There are a multitude of other potential mechanisms that may be triggered in response to a toxin at sublethal exposures. Here we present a review documenting the evidence to date on the indicators of the molecular response to nanomaterials from in vitro and in vivo studies. Alternative pathways as indicated by single biomarker, global gene expression studies and next generation sequencing approaches are discussed as well as the impacts of nanomaterial type, dose, and the types of system studied. Specific mechanisms that are impacted by a nanomaterial can be used as the basis of better high-throughput methods for evaluating how nanomaterial chemistry impacts toxicity and support models to predict the toxicity of future nanomaterials.

Purpose: This paper aims to generate both a theoretical and an empirical basis for a research model that serves in further research as an analytical tool for understanding the complex phenomenon of learning at different levels in a work organisation. The key concept in this model is the routine concept of Nelson and Winter.…

... These routines are written in Exelis Visual Information Solutions IDL programming language. They can be run either with a licensed ... with IDL and is available from Exelis Visual Information Solutions . The IDL VM software can be downloaded from this site or ordered ...

The acute toxicity of three obscurants was determined for nine freshwater organisms. The materials tested were white phosphorus-felt smoke, red phosphorus-butyl rubber (RP-BR) smoke, and smoke generator fuel (SGF) No. 2 fog oil (bulk and vaporized). The chemistry of WP-F and RP-BR smoke in water and the resulting effects on aquatic organisms are similar. Combustion of these two obscurants and their deposition in water leads to the formation of many complex oxy-phosphoric acids. Rates of hydrolysis of these complex products to ortho-phosphate were inconsistent and unpredictable over time. These products acidify water and produce toxic effects after exhausting the buffering capacity of the water. Acute 96 hr tests using Daphnia magna with neutralized and nonneutralized exposure solutions indicated that the presence of unidentified toxic component(s) acted independently of pH. At pH levels of 6.0 to 7.0, phosphorus combustion products precipitated out of solution leading to a bimodal toxic response in extended 96-hr tests with Daphnia magna. Most components of fog oil had low solubility in water. Saturation was apparent at approximately 0.1 to 0.3 mg/L total oil. Vaporization had no demonstrable effect on the chemistry or toxicity of the fog oil. Neither the bulk fog oil nor the vaporized fog oil was acutely toxic to freshwater animals at concentrations less than 10 mg/L total oil. In oil-water mixes in excess of 1.0 mg/L total oil, fog oil quickly separated and floated to the surface. The primary hazard associated with vaporized and bulk fog oil was the physical effect of oil fouling the organisms. Photolysis increased the concentration of water-soluble components of the fog oil. Acute toxicity was demonstrated in oil-water mixes (approx.10 mg/L total oil) of photolyzed bulk and vaporized fog oil. No difference in toxicity was observed between photolyzed and non-photolyzed dilutions of OWM at comparable levels of total oil.

Trichloroethylene (TCE) was found as a contaminant in the well supplying water to an aquatic testing laboratory. The groundwater was routinelyscreened by a commercial laboratory for volatile and semivolatile compounds, metals, herbicides, pesticides, and polychlorinated biphenyls using U.S. Environmental Protection Agency methods. Although TCE was the only reportable peak on the gas chromatograph, with average concentrations of 0.200 mg/l, other small peaks were also present, indicating the possibility that the contamination was not limited to TCE alone. A chronic 6-month carcinogenicity assay was conducted on-site in a biomonitoring trailer, using the Japanese medaka fish (Oryzias latipes) in an initiation-promotion protocol, with diethylnitrosamine (DEN) as the initiator and the TCE-contaminated groundwater as a promoter. Study results indicated no evidence of carcinogenic potential of the groundwater without initiation. There was, however, a tumor-promotional effect of the groundwater after DEN initiation. A follow-up laboratory study was conducted using reagent grade TCE added to carbon-filtered groundwater to simulate TCE concentrations comparable to those found in the contaminated groundwater. Study results indicated no promotional effects of TCE. These studies emphasize the necessity for on-site bioassays to assess potential environmental hazards. In this instance, chemical analysis of the groundwater identified TCE as the only reportable contaminant, but other compounds present below reportable limits were noted and may have had a synergistic effect on tumor promotion observed with the groundwater exposure. Laboratory toxicity testing of single compounds can produce toxicity data specific to that compound for that species but cannot take into account the possible toxic effects of mixtures of compounds.

Trichloroethylene (TCE) was found as a contaminant in the well supplying water to an aquatic testing laboratory. The groundwater was routinelyscreened by a commercial laboratory for volatile and semivolatile compounds, metals, herbicides, pesticides, and polychlorinated biphenyls using U.S. Environmental Protection Agency methods. Although TCE was the only reportable peak on the gas chromatograph, with average concentrations of 0.200 mg/l, other small peaks were also present, indicating the possibility that the contamination was not limited to TCE alone. A chronic 6-month carcinogenicity assay was conducted on-site in a biomonitoring trailer, using the Japanese medaka fish (Oryzias latipes) in an initiation-promotion protocol, with diethylnitrosamine (DEN) as the initiator and the TCE-contaminated groundwater as a promoter. Study results indicated no evidence of carcinogenic potential of the groundwater without initiation. There was, however, a tumor-promotional effect of the groundwater after DEN initiation. A follow-up laboratory study was conducted using reagent grade TCE added to carbon-filtered groundwater to simulate TCE concentrations comparable to those found in the contaminated groundwater. Study results indicated no promotional effects of TCE. These studies emphasize the necessity for on-site bioassays to assess potential environmental hazards. In this instance, chemical analysis of the groundwater identified TCE as the only reportable contaminant, but other compounds present below reportable limits were noted and may have had a synergistic effect on tumor promotion observed with the groundwater exposure. Laboratory toxicity testing of single compounds can produce toxicity data specific to that compound for that species but cannot take into account the possible toxic effects of mixtures of compounds. Images Figure 2 PMID:9860885

A screening level risk assessment has been performed for tertiary-butyl acetate (TBAC) examining its primary uses as a solvent in industrial and consumer products. Hazard quotients (HQ) were developed by merging TBAC animal toxicity and dose-response data with population-level, occupational and consumer exposure scenarios. TBAC has a low order of toxicity following subchronic inhalation exposure, and neurobehavioral changes (hyperactivity) in mice observed immediately after termination of exposure were used as conservative endpoints for derivation of acute and chronic reference concentration (RfC) values. TBAC is not genotoxic but has not been tested for carcinogenicity. However, TBAC is unlikely to be a human carcinogen in that its non-genotoxic metabolic surrogates tertiary-butanol (TBA) and methyl tertiary butyl ether (MTBE) produce only male rat α-2u-globulin-mediated kidney cancer and high-dose specific mouse thyroid tumors, both of which have little qualitative or quantitative relevance to humans. Benchmark dose (BMD)-modeling of the neurobehavioral responses yielded acute and chronic RfC values of 1.5 ppm and 0.3 ppm, respectively. After conservative modeling of general population and near-source occupational and consumer product exposure scenarios, almost all HQs were substantially less than 1. HQs exceeding 1 were limited to consumer use of automotive products and paints in a poorly ventilated garage-sized room (HQ = 313) and occupational exposures in small and large brake shops using no personal protective equipment or ventilation controls (HQs = 3.4-126.6). The screening level risk assessments confirm low human health concerns with most uses of TBAC and indicate that further data-informed refinements can address problematic health/exposure scenarios. The assessments also illustrate how tier-based risk assessments using read-across toxicity information to metabolic surrogates reduce the need for comprehensive animal testing.

Cardiotoxicity is one of the most serious side effects of new drugs. Early detection of the drug induced cardiotoxicity based on the biomarkers provides an important preventative strategy for detecting potential cardiotoxicity of candidate drugs. In this study, we aim to identify the predictive genomics biomarkers for drug-induced cardiac toxicity based on the RTCA coupled with PCR Array technology in primary cells. Three prototypical cardiotoxic compounds (doxorubicin, isoproterenol, ouabain) with different mechanisms were firstly real-time monitored to diagnose the cytotoxicity by using the RTCA, while the functional alterations of cardiomyocytes were also monitored by analyzing the beating frequency of cardiomyocytes. Then cardiac specific toxicity gene expression changes were studied by using the technology of PCR Array, which can detect the changes of 84 cardiac functions related genes. Rps6kb1 was identified to be the common cardiac biomarkers by using multivariate statistical and integration analyses. The biomarker was further verified by selecting other drugs with or without cardiotoxicity, and the results showed that the gene exhibited specific changes in cardiac toxicity. Moreover, IPA was applied to combine relevant pathways of Rps6kb1, and identify the main types of cardiac toxicity. These results would further enrich the evaluating strategy of drug-induced cardiotoxicity in vitro, and Rps6kb1 could be used as the specific biomarker of cardiotoxcity during safety assessment of the novel drug candidates.

Workers at the Energy Department's Fernald plant routinely received [open quotes]gross,[close quotes] [open quotes]unacceptable[close quotes] and [open quotes]undue[close quotes] radiation exposures during uranium processing operations from the 1950s through the early 1970s, according to internal Fernald memos. The documents come to light as DOE continues to pay hundreds of thousands of dollars every month to defend its former Fernald contractor, NLO Inc., from a workers' lawsuit seeking compensation for alleged injuries from poor safety practices at the Ohio facility. DOE officials have contended the NLO defense effort is justified because there is no evidence that any former Fernald workers have suffered injury as a result of radiation exposures at the plant. However, the internal Fernald memos document major concerns expressed by Fernald health officials about unsafe working conditions at the plant and what appear in some cases to be routine overexposures of workers.

Advances in high-throughput screening (HTS) instrumentation have led to enormous reduction of costs (e.g., of pipetting stations) and to the development of smaller instruments for automation of day-to-day routines in small research laboratories. In the biomaterials community, there has been an increasing interest for standardized screening protocols to identify cell type-specific cytocompatible biomaterials suitable for tissue engineering (TE) applications. In this study, the authors established a multiplexed assay protocol for toxicityscreening of biomaterials using a low- to medium-throughput robotic liquid handling station (LHS). The protocol contains analysis of viability, cytotoxicity, and apoptosis combined in one assay. This study includes performance results of a side-by-side comparison of the EpMotion 5070 LHS and conventional pipetting/dispensing systems. Critical parameters were optimized each for a given platform. Higher accuracy and reproducibility were achieved for LHS compared to manually treated samples. The practicability and accuracy of the method in a typical small laboratory setting were tested by running daily routine tasks by trained and untrained laboratory staff. In addition, advantages and disadvantages as well as the step-by-step application protocol are reported. The approach described provides a potential utility in screening biomaterials toxicity, allowing researchers to meet the needs of low- and medium-throughput laboratories.

A 28-day repeated oral dose toxicity study of nonylphenol (NP) was performed for an international validation of the 'Enhanced OECD Test Guideline 407' paying particular attention to the sensitivity of individual endocrine-related parameters. Sprague-Dawley rats, each group consisting of ten males and ten females, were administered NP once daily by gavage at doses of 0 (control), 10, 50, or 250 mg/kg body weight. At 250 mg/kg, three females died or became moribund during the experiment. At this dose, hepatic and renal toxicity was evident in both sexes with increase of relative liver and kidney weights as well as histopathological changes, such as centrilobular liver cell hypertrophy and a variety of renal tubular lesions, and alteration of serum biochemical parameters, some of them being evident from 50 mg/kg in females (glucose and inorganic phosphates). Hematologically, development of anemia was evident at 250 mg/kg in both sexes. Regarding endocrine-related effects, increase of thyroid weight in males was detected from 50 mg/kg. At 250 mg/kg, males exhibited reduction of relative weights of the ventral prostate and seminal vesicles, and females developed irregular estrous cyclicity and vaginal mucosal hyperplasia. Although changes in serum hormone levels were detected in both sexes, magnitude of the changes was small to be regarded as a low toxicological significance. In summary, repeated oral doses of NP to rats for 28 days resulted in hepato-renal toxicity from 50 mg/kg and anemia at 250 mg/kg. Effects on the endocrine system were observed from 50 mg/kg, and assessment of weights and histopathology of endocrine-related organs and estrous cyclicity may be valid in a battery for detecting endocrine effects of NP. The no-observed-adverse-effect level of NP was estimated to be 10 mg/kg per day.

Cyclophosphamide (CPM) is an alkylating agent widely used for the treatment of malignant neoplasia and which can be used in the treatment of multiple rheumatic diseases. Medication administration errors may lead to its reduced efficacy or increased drug toxicity. Many errors occur in the administration of injectable drugs. The present study aimed at structuring a routine for cyclophosphamide use, as well as creating a document with pharmacotherapeutic guidelines for the patient. The routine is schematized in three phases: pre-chemotherapy (pre-ChT), administration of cyclophosphamide, and post-chemotherapy (post-ChT), taking into account the drugs to be administered before and after cyclophosphamide in order to prevent adverse effects, including nausea and hemorrhagic cystitis. Adverse reactions can alter laboratory tests; thus, this routine included clinical management for changes in white blood cells, platelets, neutrophils, and sodium, including cyclophosphamide dose adjustment in the case of kidney disease. Cyclophosphamide is responsible for other rare-but serious-side effects, for instance, hepatotoxicity, severe hyponatremia and heart failure. Other adverse reactions include hair loss, amenorrhea and menopause. In this routine, we also entered guidelines to post-chemotherapy patients. The compatibility of injectable drugs with the vehicle used has been described, as well as stability and infusion times. The routine aimed at the rational use of cyclophosphamide, with prevention of adverse events and relapse episodes, factors that may burden the health care system.

There is an increasing commercial demand for various nanoparticles due to their extensive applicability in various areas such as electronics, catalysis, chemistry, energy and medicine. Metallic nanoparticles are traditionally synthesized by wet chemical techniques, where the chemicals used are quite often toxic and flammable. Fig has been a typical fruit component of the health-promoting Mediterranean diet for a very long time. In the present study, we describe a cost effective and eco-friendly technique for green synthesis of silver nanoparticles from 1 mM AgNO3 solution through the extract of dried fig (Ficus carica L.) fruit as reducing as well as capping agent. Nanoparticles were characterized using UV absorption spectroscopy and SEM. The sizes of the spherical silver particles were found to be in the range of 54-89 nm. The biologically synthesized nanoparticles also exhibited a significant cytotoxic effect on MCF7cell lines and further animal acute toxicity results state that the above AgNPs are toxicologically safe by oral administration.

This study is an adaptation of the nicotine-evoked locomotor response (NLR) assay, which was originally utilized for phenotype-based neurotoxicity screening in zebrafish embryos. Zebrafish embryos do not exhibit spontaneous swimming until roughly 4 days post-fertilization (dpf), however, a robust swimming response can be induced as early as 36 hours post-fertilization (hpf) by means of acute nicotine exposure (30–240μM). Here, the NLR was tested as a tool for early detection of locomotor phenotypes in 36, 48 and 72 hpf mutant zebrafish embryos of the non-touch-responsive maco strain; this assay successfully discriminated mutant embryos from their non-mutant siblings. Then, methylmercury (MeHg) was used as a proof-of-concept neurotoxicant to test the effectiveness of the NLR assay as a screening tool in toxicology. The locomotor effects of MeHg were evaluated in 6 dpf wild type eleutheroembryos exposed to waterborne MeHg (0, 0.01, 0.03 and 0.1μM). Afterwards, the NLR assay was tested in 48 hpf embryos subjected to the same MeHg exposure regimes. Embryos exposed to 0.01 and 0.03μM of MeHg exhibited significant increases in locomotion in both scenarios. These findings suggest that similar locomotor phenotypes observed in free swimming fish can be detected as early as 48 hpf, when locomotion is induced with nicotine. PMID:27123921

The present investigation was carried out to screen native plants growing in fly-ash (FA) contaminated areas near National Thermal Power Corporation, Tanda, Uttar Pradesh, India with a view to using them for the eco-restoration of the area. A total number of 17 plants (9 aquatic, 6 terrestrial and 2 algal species) were collected and screened for heavy metal (Fe, Zn, Cu, Mo, B, Si, Al, Cr, Pb, Cd, Hg and As) accumulation. Differential accumulation of various heavy metals by different species of plants was observed. Hydrilla verticillata was found to be the most efficient metal accumulator among 9 aquatic plants, Eclipta alba among 6 terrestrial plants and Phormedium papyraceum between 2 algal species. In general, the maximum levels of most metals were found in terrestrial plants while the lowest in algal species. However, translocation of the metals from root to shoot was found to be higher in aquatic plants than terrestrial ones. These results suggest that various aquatic, terrestrial and algal species of plants may be used in a synergistic way to remediate and restore the FA contaminated areas.

GABAARs and GlyRs are considered attractive drug targets for therapeutic intervention and are also increasingly recognized in the context of in vitro neurotoxicity (NT) and developmental neurotoxicity (DNT) testing. However, systematic human-specific GABAAR and GlyR-targeted drug screening and toxicity testing is hampered due to lack of appropriate in vitro models that express native GABAARs and GlyRs. We have established a human pluripotent stem cell line (NT2) stably expressing YFP-I152L, a halide-sensitive variant of yellow fluorescent protein (YFP), allowing for fluorescence-based functional analysis of chloride channels. Upon stimulation with retinoic acid, NT2 cells undergo neuronal differentiation and allow pharmacological and toxicological evaluation of native GABAARs and GlyRs at different stages of brain maturation. We applied the cell line in concentration-response experiments with the neurotransmitters GABA and glycine as well as with the drugs strychnine, picrotoxin, fipronil, lindane, bicuculline, and zinc and demonstrate that the established in vitro model is applicable to GABAAR and GlyR-targeted pharmacological and toxicological profiling. We quantified the proportion of GABAAR and GlyR-sensitive cells, respectively, and identified percentages of approximately 20% each within the overall populations, rendering the cells a suitable model for systematic in vitro GABAAR and GlyR-targeted screening in the context of drug development and NT/DNT testing. PMID:27445687

Toxic hepatitis Overview By Mayo Clinic Staff Toxic hepatitis is an inflammation of your liver in reaction to certain substances to which you're exposed. Toxic hepatitis can be caused by alcohol, chemicals, drugs or ...

Colorectal carcinoma is a common cause of death throughout the world and may be prevented by routine control, which can detect precancerous neoplasms and early cancers before they undergo malignant transformation or metastasis. Three strategies may improve colon cancer screening rates: convince the population about the importance of undergoing a screening test; achieve higher efficacy in standard screening tests and make them more available to the community and develop new more sensitive and efficacious screening methods and make them available as routine tests. In this light, the present study seeks to review these three means through which to increase colon cancer screening rates. PMID:26688708

A series of range finding studies were accomplished in order to economically mass produce the embryos of the annual killifish, Nothobranchius cruentheri. Survival of embryos was found to increase dramatically with increasing the sodium chloride concentration from 0.6 to 4.0 parts per thousand. The chorion strength increased with increasing salt concentration as well. Techniques were established to allow long term storage of Diapause III embryos for use in rapid toxicity test systems developed at the Research Methods Branch of the U.S. Army Biomedical Research and Development Lab. Established techniques allowed for the production of 500,000 or more eggs/per month. At the highest salt concentrations, embryos were able to survive out of water for 90 days while remaining in Diapause III, a prehatching arrest.

Pitfalls in the method for demonstrating antinuclear antibodies (ANA) by the indirect immunofluorescence technique are described and the use of international standard preparations outlined. Determination of the optimal border dilution dividing positive from negative results is discussed. Each laboratory is a unique setting; it must define its own method, which should rarely be changed. One should not rely on copying methods from other laboratories or commercial firms, but the reproducibility of the nuclear substrate, the conjugate, and other variables should be controlled daily by the use of a control serum which has been related to the WHO standard preparation for ANA of the homogeneous type. Since many sera contain mixtures of different ANA, the results of routine tests are best expressed in titres or expressions of the intensity of fluorescence. The ANA test using the immunofluorescence technique should be used as a screening method for other tests allowing a more defined interpretation of the ANA. Each laboratory should individually determine the border between positive and negative results. Therefore about 200 sera from local healthy controls equally distributed over sex and age, and 100 sera from local patients with definite SLE should be tested. Since the local clinicians should become acquainted with this border it should rarely be changed. Finally each laboratory should participate regularly in national and international quality control rounds, where sera known to be difficult to interpret are tested. The judgment of the organisers of these rounds should stimulate improvements in the participating laboratories. PMID:8984936

Pitfalls in the method for demonstrating antinuclear antibodies (ANA) by the indirect immunofluorescence technique are described and the use of international standard preparations outlined. Determination of the optimal border dilution dividing positive from negative results is discussed. Each laboratory is a unique setting; it must define its own method, which should rarely be changed. One should not rely on copying methods from other laboratories or commercial firms, but the reproducibility of the nuclear substrate, the conjugate, and other variables should be controlled daily by the use of a control serum which has been related to the WHO standard preparation for ANA of the homogeneous type. Since many sera contain mixtures of different ANA, the results of routine tests are best expressed in titres or expressions of the intensity of fluorescence. The ANA test using the immunofluorescence technique should be used as a screening method for other tests allowing a more defined interpretation of the ANA. Each laboratory should individually determine the border between positive and negative results. Therefore about 200 sera from local healthy controls equally distributed over sex and age, and 100 sera from local patients with definite SLE should be tested. Since the local clinicians should become acquainted with this border it should rarely be changed. Finally each laboratory should participate regularly in national and international quality control rounds, where sera known to be difficult to interpret are tested. The judgment of the organisers of these rounds should stimulate improvements in the participating laboratories.

... news/fullstory_162856.html Routine Checkup Should Assess Fitness, Too Cardiorespiratory test would help gauge patients' heart ... checked regularly, but an exercise expert says cardiorespiratory fitness should also be part of a routine medical ...

Program sustainability is an ongoing concern for most people in health promotion. However, the current notion of sustainability in organizations, namely routinization, needs refinement. This article examines organizational routines. In so doing, it refines the notion of sustainability and the assessment of routines. Drawing on the organizational literature, a routinized program is defined by the presence of routinized activities, meaning that these activities exhibit four characteristics of organizational routines: memory, adaptation, values and rules. To answer the question of how these characteristics are useful, we conducted an empirical study of the routinization of the Quebec Heart Health Demonstration Project in five community health centers. Our method consisted of a multiple-case study. We observed project activities in each center in 2000. The data came from documents and interviews with project actors. Our results show that, in one of the centers, no resources had been officially committed to project activities. Even so, the actors continued some activities on an informal basis. In another center, the activities satisfied three of the four routine characteristics. In the three others, activities satisfied all of the characteristics. These results suggest focusing the study of program sustainability on the routinization of activities resulting from it. They indicate four distinct degrees of sustainability: (1) the absence of sustainability; no program activity is continued; (2) precarious sustainability; some residual activities are pursued, at least unofficially; (3) weak sustainability; the program produces some official activities that are not routinized; and (4) sustainability through routinization; routinized activities result from the program.

This dissertation explores the effects of increased digitization on the evolutionary dynamics of organizational routines. Do routines become more flexible, or more rigid, as the mix of digital technologies and human actors changes? What are the mechanisms that govern the evolution of routines? The dissertation theorizes about the effects of…

The goal of this study was to prepare nontoxic, biomimetic TiO2/chondroitin-4-sulfate nanocomposites with osteointegration ability for biomedical applications. Nanocomposites with higher surface area were subjected to bioactivity study and obtained bone-like layer with stoichiometric Ca/P ratio of 1.64 and 1.66. The susceptibility of nanocomposites against Staphylococcus aureus (∼16 mm) and Escherichia coli (∼12 mm) is favorable in preventing the risk of bone diseases and postoperative infections. Adequate swelling and degradations properties were favorably achieved to reduce the risk of nanoparticle accumulation in cell organelles. Moreover, the toxicity in AGS cell line and biocompatibility in osteoblast-like MG-63 cell line showed no significant mitochondrial damage. In addition, the in vitro expression of osteoblast inducing genes (OCN, OPN, ALP and COL 1) and their up-regulation, and 20% of increased hatching rate in preliminary in vivo (zebrafish) analysis were favorable for the nanocomposite at the ratio of 2:0.50 than pure TiO2. Hence, it can be concluded that among the prepared nanocomposites TCs.5 is a promising biomimetic biomaterial that can be used for advanced orthopedic research and other applications.

In 1974, the World Health Organization (WHO) established the Expanded Program on Immunization* to provide protection against six vaccine-preventable diseases through routine infant immunization (1). Based on 2015 WHO and United Nations Children's Fund (UNICEF) estimates, global coverage with the third dose of diphtheria-tetanus-pertussis vaccine (DTP3), the first dose of measles-containing vaccine (MCV1) and the third dose of polio vaccine (Pol3) has remained stable (84%-86%) since 2010. From 2014 to 2015, estimated global coverage with the second MCV dose (MCV2) increased from 39% to 43% by the end of the second year of life and from 58% to 61% when older age groups were included. Global coverage was higher in 2015 than 2010 for newer or underused vaccines, including rotavirus vaccine, pneumococcal conjugate vaccine (PCV), rubella vaccine, Haemophilus influenzae type b (Hib) vaccine, and 3 doses of hepatitis B (HepB3) vaccine. Coverage estimates varied widely by WHO Region, country, and district; in addition, for the vaccines evaluated (MCV, DTP3, Pol3, HepB3, Hib3), wide disparities were found in coverage by country income classification. Improvements in equity of access are necessary to reach and sustain higher coverage and increase protection from vaccine-preventable diseases for all persons.

Canada is a federal country of 10 provinces and three territories. High level information on mental health conditions and service use has mostly been generated from administrative data collected by provinces and territories. These include four major types - hospital admissions and discharges, physician billings, ambulatory care services, and drug databases. At the national level, the Canadian Institute for Health Information brings together this information to produce indicators of outcome. Although these data provide information on patient and health system characteristics, they do not capture the full spectrum of formal and informal mental healthcare. These include changes in health status, functioning, community integration and quality of life. As a result, some jurisdictions have begun to implement more standardized measures of outcome such as the clinician-rated Health of the Nation Outcome Scales or the inpatient Resident Assessment Instrument - Mental Health. In this paper we provide an overview of mental-health-related data sources in Canada, highlight some of the more progressive practices beginning to emerge, and conclude with some thoughts about how the routine measurement and reporting of mental health outcomes in Canada might be advanced including efforts at engaging both clinicians and decision-makers.

Background Genome instability is a main cause of chromosomal alterations in both somatic and germ cells when exposed to environmental, physical and chemical genotoxicants. Germ cells especially spermatozoa are more vulnerable to suffering from DNA damaging agents during spermatogenesis and also more potent in transmitting genome instability to next generation. Methods To investigate the effects of γ-rays on inducing abnormalities manifested as numerical Chromosome Aberrations (CA) and Micronucleus (MN) in preimplantation embryos, adult male NMRI mice were irradiated with 4 Gy of γ-rays. They were then mated at weekly intervals with superovulated, non-irradiated female mice in 6 successive weeks. About 68 hr post coitous, four to eight cell embryos were retrieved and fixed on slides using standard methods in order to screen for CA and MN. Results In embryos generated from irradiated mice, the frequency of aneuploidy and MN increased dramatically at all post-irradiation sampling times as compared to the control (p<0.01). The frequency of embryos expressed MN was much higher than chromosomally abnormal embryos, although the trend of MN formation was similar to chromosomal abnormalities seen in corresponding sampling times. Conclusion Irradiation of sperms at any stages of spermatogenesis may lead to stable chromosomal abnormalities affecting pairing and disjunction of chromosomes in successive preimplantation embryos that are expressed as MN. Although chromosome analysis of embryos showed various types of chromosomal abnormalities, MN assay provide a simpler and faster technique for investigating the genotoxicity of agents affecting embryos at preimplantation stages. PMID:25215176

The overall objective of this project is to study the feasibility of using and evanescent field absorbance sensor Fourier transform infrared (EFAS FT-IR) spectroscopic sensor coupled with cone penetrometry (CPT) as a field screening method. The specific objectives of this project are as follows: design an accessory for use with FT-IR that interfaces the spectrometer to a cone penetrometer; characterize the response of the FT-IR accessory to selected hydrocarbons in a laboratory-simulated field environment; and determine the ability of the FT-IR-CPT instrument to measure hydrocarbon contamination in soil by direct comparison with a reference method (e.g., Soxhlet extraction followed by gas chromatography) to quantify hydrocarbon from the same soil. Work performed during the second two quarters was focused on three areas: characterization of a candidate polymeric film for use in solid-phase microextraction (SPME) of analytes onto the sensor; evaluation of EFAS design; and development of a conceptual design for a spectroscopic sensor.

Abstract Clinicians who routinely take patient sexual histories have the opportunity to assess patient risk for sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV), and make appropriate recommendations for routine HIV/STD screenings. However, less than 40% of providers conduct sexual histories with patients, and many do not receive formal sexual history training in school. After partnering with a national professional organization of physicians, we trained 26 (US and US territory-based) practicing physicians (58% female; median age=48 years) regarding sexual history taking using both in-person and webinar methods. Trainings occurred during either a 6-h onsite or 2-h webinar session. We evaluated their post-training experiences integrating sexual histories during routine medical visits. We assessed use of sexual histories and routine HIV/STD screenings. All participating physicians reported improved sexual history taking and increases in documented sexual histories and routine HIV/STD screenings. Four themes emerged from the qualitative evaluations: (1) the need for more sexual history training; (2) the importance of providing a gender-neutral sexual history tool; (3) the existence of barriers to routine sexual histories/testing; and (4) unintended benefits for providers who were conducting routine sexual histories. These findings were used to develop a brief, gender-neutral sexual history tool for clinical use. This pilot evaluation demonstrates that providers were willing to utilize a sexual history tool in clinical practice in support of HIV/STD prevention efforts. PMID:24564387

In case of incidental confinement failure, mixed oxide (MOX) fuel preparation may expose workers to plutonium aerosols. Due to its potential toxicity, occupational exposure to plutonium compounds should be kept as low as reasonably achievable. To ensure the absence of significant intake of radionuclides, workers at risk of internal contamination are monitored by periodic bioassay planned in a routine monitoring programme. From bioassay results, internal dose may be estimated. However, accurate dose calculation relies on known exposure conditions, which are rarely available when the exposure is demonstrated by routine monitoring only. Therefore, internal dose calculation is subject to uncertainty from unknown exposure conditions and from activity measurement variability. The present study calculates the minimum detectable dose (MDD) for a routine monitoring programme by considering all plausible conditions of exposure and measurement uncertainty. The MDD evaluates the monitoring quality and can be used for optimization. Here, MDDs were calculated for the monitoring of workers preparing MOX fuel. Uncertain parameters were modelled by probability distributions defined according to information provided by experts of routine monitoring, of workplace radiological protection and of bioassay analysis. Results show that the current monitoring is well adapted to potential exposure. A sensitivity study of MDD highlights high dependence on exposure condition modelling. Integrating all expert knowledge is therefore crucial to obtain reliable MDD estimates, stressing the value of a holistic approach to worker monitoring.

Toxicology can no longer be used only as a science that reacts to problems but must be more proactive in predicting potential human safety issues with new drug candidates. Success in this area must be based on an understanding of the mechanisms of toxicity. This review summarizes and extends some of the concepts of an American Chemical Society ProSpectives meeting on the title subject held in June 2006. One important area is the discernment of the exact nature of the most common problems in drug toxicity. Knowledge of chemical structure alerts and relevant biological pathways are important. Biological activation to reactive products and off-target pharmacology are considered to be major contexts of drug toxicity, although defining exactly what the contributions are is not trivial. Some newer approaches to screening for both have been developed. A goal in predictive toxicology is the use of in vitro methods and database development to make predictions concerning potential modes of toxicity and to stratify drug candidates for further development. Such predictions are desirable for several economic and other reasons but are certainly not routine yet. However, progress has been made using several approaches. Some examples of the application of studies of wide-scale biological responses are now available, with incorporation into development paradigms.

Many daily routines and behaviors are related to the prevalence of obesity. This study investigated the association between routines and behaviors that act as protective factors related to lower prevalence of obesity in parents (BMI ≥ 30 kg/m(2)) and overweight in preschool children (BMI ≥ 85th percentile). Socio-demographic characteristics were assessed in relation to protective routines (PRs), and prevalence of obesity/overweight data from 337 preschool children and their parents. The two PRs assessed with parents included adequate sleep (≥7 h/night) and family mealtime routine (scoring higher than the median score). The four PRs assessed in children included adequate sleep (≥10 h/night), family mealtime routine, limiting screen-viewing time (≤2 h/day of TV, video, DVD), and not having a bedroom TV. Overall, 27.9% of parents were obese and 22.8% of children were overweight, and 39.8% of the parents had both parent PRs, and only 11.6% of children had all four child PRs. Results demonstrated that several demographic factors were significantly related to the use of PRs for parents and children. The lack of PRs was related to increased risk for overweight in children, but not for obesity in parents. However, in the adjusted models the overall cumulative benefits of using PRs was not significant in children either. In the multivariate adjusted logistic regression models, the only significant individual PR for children was adequate sleep. In a path analysis model, parent sleep was related to child sleep, which was in turn related to decreased obesity. Overall, findings suggest that parent and child PRs, especially sleep routines, within a family can be associated and may play an important role in the health outcomes of both parents and children. Understanding the mechanisms that influence how and when parents and children use these PRs may be promising for developing targeted family-based obesity-prevention efforts.

The bacteriophage lambda replication initiation protein P exhibits a toxic effect on its Escherichia coli (E. coli) host, likely due to the formation of a dead-end P-DnaB complex, sequestering the replicative DnaB helicase from further activity. Intracellular expression of P triggers SOS-independent cellular filamentation and rapidly cures resident ColE1 plasmids. The toxicity of P is suppressed by alleles of P or dnaB. We asked whether P buildup within a cell can influence E. coli replication fidelity. The influence of P expression from a defective prophage, or when cloned and expressed from a plasmid was examined by screening for auxotrophic mutants, or by selection for rifampicin resistant (RifR) cells acquiring mutations within the rpoB gene encoding the β-subunit of RNA polymerase (RNAP), nine of which proved unique. Using fluctuation assays, we show that the intracellular expression of P evokes a mutator effect. Most of the RifR mutants remained PS and localized to the Rif binding pocket in RNAP, but a subset acquired a PR phenotype, lost sensitivity to ColE1 plasmid curing, and localized outside of the pocket. One PR mutation was identical to rpo*Q148P, which alleviates the UV-sensitivity of ruv strains defective in the migration and resolution of Holliday junctions and destabilizes stalled RNAP elongation complexes. The results suggest that P-DnaB sequestration is mutagenic and supports an earlier observation that P can interact with RNAP. PMID:27338450

The machinery of translation is one of the most common targets of antibiotics. The development and screening of new antibiotics usually proceeds by testing antimicrobial activity followed by laborious studies of the mechanism of action. High-throughput methods for new antibiotic screening based on antimicrobial activity have become routine; however, identification of molecular targets is usually a challenge. Therefore, it is highly beneficial to combine primary screening with the identification of the mechanism of action. In this review, we describe a collection of methods for screening translation inhibitors, with a special emphasis on methods which can be performed in a high-throughput manner. PMID:27348012

Irinotecan is a major drug in the treatment of advanced colorectal cancer. Its active form is the SN38 metabolite, which is cleared by the biliary route after glucuronidation by uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1). UGT1A1 activity exhibits a wide intersubject variability, in part related to UGT1A1 gene polymorphisms. The present review on the impact of the deficient UGT1A1*28 variant on irinotecan efficacy and toxicity was produced by a French joint workgroup comprising the Group of Clinical Onco-pharmacology (GPCO-Unicancer) and the National Pharmacogenetics Network (RNPGx). It clearly emerges that for irinotecan doses at least equal to 180 mg/m(2) , patients homozygous for the UGT1A1*28 allele are at increased risk of developing hematological and/or digestive toxicities. Irinotecan dose reduction is thus recommended in homozygous *28/*28 patients. In addition, this personalized medicine strategy aims to secure high-dose irinotecan administration (≥240 mg/m(2) ) that have proven to be safe in homozygous *1/*1 patients only. The clinical relevance of this test is discussed in terms of treatment efficacy improvement, as increasing the irinotecan dose appears to be safe in patients not bearing a deficient allele. Best execution practices, cost-effectiveness, and result interpretation are discussed with the aim of facilitating the implementation of this analysis in clinical practice. The existence of networks of laboratories performing this test in routine hospital treatment, as in France, offers the prospect of widespread screening, thus guaranteeing equal access to safe treatment and optimized therapy for patients receiving irinotecan-based therapy in advanced colorectal cancer.

AIM To investigate the cost effectiveness of routine small bowel biopsies (SBBs) in patients with iron deficiency anemia (IDA) independent of their celiac disease (CD) serology test results. METHODS We used a state transition Markov model. Two strategies were compared: routine SBBs during esophagogastroduodenoscopy (EGD) in all patients with IDA regardless their celiac serology status (strategy A) vs SBBs only in IDA patients with positive serology (strategy B). The main outcomes were quality adjusted life years (QALY), average cost and the incremental cost effectiveness ratio (ICER). One way sensitivity analysis was performed on all variables and two way sensitivity analysis on selected variables were done. In order to validate the results, a Monte Carlo simulation of 100 sample trials with 10, and an acceptability curve were performed. RESULTS Strategy A of routine SBBs yielded 19.888 QALYs with a cost of $218.10 compared to 19.887 QALYs and $234.17 in strategy B. In terms of cost-effectiveness, strategy A was the dominant strategy, as long as the cost of SBBs stayed less than $67. In addition, the ICER of strategy A was preferable, providing the cost of biopsy stays under $77. Monte Carlo simulation demonstrated that strategy A yielded the same QALY but with lower costs than strategy B. CONCLUSION Our model suggests that EGD with routine SBBs is a cost-effective approach with improved QALYs in patients with IDA when the prevalence of CD is 5% or greater. SBBs should be a routinescreening tool for CD among patients with IDA, regardless of their celiac antibody status. PMID:27678365

This article presents warm-ups that are designed to physiologically and psychologically prepare students for vigorous physical activity. An active movement warm-up routine is made up of three parts: (1) active warm-up movement exercises, (2) general preparation, and (3) the energy system. These warm-up routines can be used with all grade levels…

This document describes a set of routines for a VME DMA module called the Super-VIOR. The Super-VIOR interface routines, also called the SVI routines, are written in PILS and run under a Valet-plus system. These routines enable a program to set up, execute, and monitor DMA operations. The Super-VIOR Interface Routines are written in PILS, a high level language similar to BASIC and Pascal which is powerful and fast enough for most applications. One of the most powerful features of the Valet/PILS system is the ability to set up exception vectors and exception handlers directly in a program. This feature is used to handle interrupts from the MC68450 (a 4 channel, 16 bit DMA controller) and the interface's front panel. This document is divided into ten sections, the first being the introduction. The remaining sections detail the interface registers, channel initiation, polling and interrupts, status reporting, front panel interrupts, the configuration routines, the operation control routines, the status reporting routines, and special comments on the MC68450.

This pilot study of the structural characteristics of daily routines of young children also explored aspects of conceptual framework and research instruments. Four data collection instruments were developed. Two of the three retrospective measures used were questionnaires for mothers about their child's routine on the previous day. The other…

Purpose: The purpose of this two-part paper is to develop a process model of unlearning established organizational routines. The model traces the interactions among three unlearning sub-processes: ostensive aspects of initial destabilization of an established routine; performative aspects of ongoing discarding-from-use of old behaviors and…

A survey of 48 United States and 9 Canadian undergraduate dental school clinics investigated the extent of routine use of screening blood tests for patients, test types used, and plans to increase or decrease screening test use. Six responded that they routinely test asymptomatic patients, with 2-20 tests used per patient. (MSE)

Routine nutritional screening of patients admitted to the surgical services confirms a substantial prevalence of malnutrition. Identification of the malnourished patient and the patient who is likely to become malnourished should be done as early as possible in the hospital stay and usually requires only simple, readily available parameters. Nutritional screening is only the first step in the optimal nutritional management of surgical patients. This information should be used to determine the need for further nutritional assessment, the appropriate consultation, and nutritional therapy.

There is no clear consensus among state newborn screening programs on whether routine second screening of newborns identifies clinically relevant cases of congenital adrenal hyperplasia. This retrospective study evaluated laboratory practices, along with biochemical and medical characteristics of congenital adrenal hyperplasia (CAH) cases (1) detected on the first newborn screen in one-screen compared to two-screen states, and (2) detected on the first versus the second screen in the two-screen states, to determine the effectiveness of a second screen. A total of 374 confirmed cases of CAH from 2 one-screen states and 5 two-screen states were included in this study. Demographic data and diagnostic information on each reported case were collected and analyzed. Additionally, laboratory data, including screening methodologies and algorithms, were evaluated. The one-screen states reported 99 cases of CAH out of 1,740,586 (1 in 17,500) newborns screened: 88 (89%) identified on first screen and 5 (5%) identified on targeted second screen. The two-screen states reported 275 cases of CAH out of 2,629,627 (1 in 9,500) newborns screened: 165 (60%) identified on first screen and 99 (36%) identified on second screen. Using a multivariate model, the only significant predictor of whether a case was identified on the first or second screen in the two-screen states was the type of CAH. Compared with classical salt-wasting CAH, classical simple virilizing and non-classical CAH cases were less likely to be detected on the first versus the second screen. The routine second newborn screen is important for identifying children with CAH, particularly simple virilizing and non-classical forms, which might otherwise not be captured through a single screen. PMID:26296712

Infobuttons have been proven as an effective means for providing quick, context-specific links to pertinent information resources at the point of care. Current infobutton manager implementations, however, lack the ability to exchange metadata, are limited to a relatively small set of information providers, and are targeted primarily for a clinician audience. As part of a local effort to implement infobuttons for patient use via a tethered personal health record, we present a series of metadata extraction routines. These routines were constructed to extract key pieces of information from health information providers on the Internet, including content coverage, language availability, and readability scores. The extraction routines were tested using thirty different disease conditions against eight different providers. The routines yielded 183 potential infobutton targets and associated metadata for each. The capabilities of the extraction routines will be expanded to cover new types of metadata in the future.

Several neurodevelopmental disorders are associated with preference for routine and challenging behavior following changes to routines. We examine individuals with Prader-Willi syndrome, who show elevated levels of this behavior, to better understand how previous experience of a routine can affect challenging behavior elicited by disruption to…

Pentachlorophenol (PCP) and its sodium salt (Na-PCP) are extremely toxic chemicals responsible for important soil and groundwater pollution, mainly caused by wastes from wood-treatment plants, because chlorinated phenols are widely used as wood preservatives. The methods most commonly used for routine analysis of pesticides such as PCP and Na-PCP are high-performance liquid chromatography (HPLC) and gas chromatography-mass spectroscopy (GC-MS). A variety of rapid biological screening tests using marine organisms, bioluminescent bacteria, and enzymes have also been reported. In this study, rapid biological screening analysis using Bacillus subtilis was developed, to assess the biodegradation of PCP and its by-products in liquid samples. An empirical model is proposed for spectrophotometric analysis of Na-PCP concentration after growth of Bacillus subtilis.

Aminophylline therapy has undergone change in the past decade. With the changes in usage and dosage forms, the frequency of toxicity in the pediatric population, especially in adolescents, has increased dramatically. Two distinct patterns, chronic and acute, have been recognized and treatment methods for both are changing. Table 4 summarizes the emerging state-of-the-art therapy for aminophylline toxicity. Judging from the activity seen in the literature, investigation into aminophylline toxicity will continue to be a priority. We will see a greater understanding of the disease process and a refining of the therapeutic process. The ultimate goal is the elimination of mortality and the minimization of morbidity from aminophylline toxicity.

Local anesthetics are the most commonly used drugs in dentistry. The number of adverse reactions reported, particularly toxic reactions, are extraordinarily negligible. This article reports a case of lidocaine toxicity with its typical manifestation in a 37-yr-old healthy male. The toxic reaction followed transoral/transpharyngeal topical spraying of lidocaine preoperatively during preparation for general anesthesia. A review of dosages of the most commonly used local anesthetic drugs in dentistry and the management of a toxic reaction is presented. Clinicians need to be in a position to recognize and successfully manage this potential adverse reaction.

Groups, like individuals, often develop habitual routines for dealing with frequently encountered stimuli. Although such routines are consequential for group life and work, little is known about them. This paper reconnoiters the territory of habitual behavior in groups that perform work within organizations. We offer a definition of group habits, identify their functions and dysfunctions, suggest how they develop and are maintained, and identify the circumstances when they are likely to be altered or abandoned. Throughout, we give special attention to the social nature of habitual routines in groups, to the interaction between habitual behavior and group life cycle phenomena, and to the role of the organizational context in prompting, shaping, and terminating habitual routines.

... page: //medlineplus.gov/ency/patientinstructions/000613.htm Taking medicine at home - create a routine To use the ... teeth. Find Ways to Help You Remember Your Medicines You can: Set the alarm on your clock, ...

This article schematically reviews the clinical features, diagnostic approaches to, and toxicological implications of toxic encephalopathy. The review will focus on the most significant occupational causes of toxic encephalopathy. Chronic toxic encephalopathy, cerebellar syndrome, parkinsonism, and vascular encephalopathy are commonly encountered clinical syndromes of toxic encephalopathy. Few neurotoxins cause patients to present with pathognomonic neurological syndromes. The symptoms and signs of toxic encephalopathy may be mimicked by many psychiatric, metabolic, inflammatory, neoplastic, and degenerative diseases of the nervous system. Thus, the importance of good history-taking that considers exposure and a comprehensive neurological examination cannot be overemphasized in the diagnosis of toxic encephalopathy. Neuropsychological testing and neuroimaging typically play ancillary roles. The recognition of toxic encephalopathy is important because the correct diagnosis of occupational disease can prevent others (e.g., workers at the same worksite) from further harm by reducing their exposure to the toxin, and also often provides some indication of prognosis. Physicians must therefore be aware of the typical signs and symptoms of toxic encephalopathy, and close collaborations between neurologists and occupational physicians are needed to determine whether neurological disorders are related to occupational neurotoxin exposure. PMID:23251840

There is emerging evidence that tungsten has toxic health effects. We summarize the recent tungsten toxicity research in this short review. Tungsten is widely used in many commercial and military applications because it has the second highest melting temperature of any element. Consequently, it is important to elucidate the potential health effects of tungsten.

New Microtox® toxicity data of 16 ionic liquids of different cationic and anionic composition were determined. The ionic liquids 1-butyl-1-methylpyrrolidinium trifluoromethanesulfonate, [BMPyr(+)][TFO(-)], 1-butyl-1-methylpyrrolidinium chloride, [BMPyr(+)][Cl(-)], hydroxypropylmethylimidazolium fluoroacetate, [HOPMIM(+)][FCH2COO(-)], and hydroxypropylmethylimidazolium glycolate [HOPMIM(+)][glycolate(-)] were found to be less toxic than conventional organic solvent such as chloroform or toluene, accoding the Microtox® toxicity assays. The toxicity of pyrrolidinium cation was lower than the imidazolium and pyridinium ones. It was found that the inclusion of an hydroxyl group in the alkyl chain length of the cation also reduce the toxicity of the ionic liquid. To sum up, the Microtox® toxicity assays can be used as screening tool to easily determined the toxicity of a wide range of ionic liquids and the toxicity data obtained could allow the obtention of structure-toxicity relationships to design less toxic ionic liquids.

Maternal markers are widely used to screen for fetal neural tube defects (NTDs), chromosomal abnormalities and cardiac defects. Some are beginning to broaden prenatal screening to include pregnancy complications such as pre-eclampsia. The methods initially developed for NTDs using a single marker have since been built upon to develop high performance multi-maker tests for chromosomal abnormalities. Although cell-free DNA testing is still too expensive to be considered for routine application in public health settings, it can be cost-effective when used in combination with existing multi-maker marker tests. The established screening methods can be readily applied in the first trimester to identify pregnancies at high risk of pre-eclampsia and offer prevention though aspirin treatment. Prenatal screening for fragile X syndrome might be adopted more widely if the test was to be framed as a form of maternal marker screening. PMID:26237388

The scope of screening is to identify disease in a clinically inapparent stage in order to treat more effectively. However, the required application of a test to large subsets of the population implies risks which cannot be ignored. Thus, the introduction of a test for use in screening without previously established evidence of a benefit which exceeds potential harm by far cannot be justified. With regard to cancer, evidence of effectiveness has been proven for screening on cervical (Papsmear), breast (mammography) and colorectal (faecal occult blood test) cancer. The routine application of a screening procedure which has been proven effective provides the benefit in terms of mortality reduction seen in the trials only if the entire screening chain, from the test over potentially required assessment to treatment, is offered with highest quality and is under permanent quality control.

Screenings are tests that look for diseases before you have symptoms. Screening tests can find diseases early, when they're easier ... Overweight and obesity Prostate cancer in men Which tests you need depends on your age, your sex, ...

The routine of subjective refraction is usually understood, explained and taught in terms of the relative positions of line or point foci and the retina. This paper argues that such an approach makes unnecessary and sometimes invalid assumptions about what is actually happening inside the eye. The only assumption necessary in fact is that the subject is able to guide the refractionist to (or close to) the optimum power for refractive compensation. The routine works even in eyes in which the interval of Sturm does not behave as supposed; it would work, in fact, regardless of the structure of the eye. The idealized subjective refraction routine consists of two steps: the first finds the best sphere (the stigmatic component) and the second finds the remaining Jackson cross-cylinder (the antistigmatic component). The model makes use of the concept of symmetric dioptric power space. The second part of the refraction routine can be performed with Jackson cross-cylinders alone. However, it is usually taught and practiced using spheres, cylinders and Jackson cross-cylinders in a procedure that is not easy to understand and learn. Recognizing that this part of the routine is equivalent to one involving Jackson cross-cylinders only allows one to teach and understand the procedure more naturally and easily.

Many researchers in the field of time-relevant, on-line toxicity monitors for source water protection believe that some mechanism to guide and prioritize research in this emerging field would be beneficial. On-line toxicity monitors are tools designed to screen water quality and ...

The U.S. Department of Energy manages the Nevada Test Site in a manner that meets evolving DOE Missions and responds to the concerns of affected and interested individuals and agencies. This Routine Radiological Monitoring Plan addressess complicance with DOE Orders 5400.1 and 5400.5 and other drivers requiring routine effluent monitoring and environmental surveillance on the Nevada Test Site. This monitoring plan, prepared in 1998, addresses the activities conducted onsite NTS under the Final Environmental Impact Statement and Record of Decision. This radiological monitoring plan, prepared on behalf of the Nevada Test Site Landlord, brings together sitewide environmental surveillance; site-specific effluent monitoring; and operational monitoring conducted by various missions, programs, and projects on the NTS. The plan provides an approach to identifying and conducting routine radiological monitoring at the NTS, based on integrated technical, scientific, and regulatory complicance data needs.

Although pilot-controller communication is central to aviation safety, this area of aviation human factors has not been extensively researched. Most research has focused on what kinds of communication problems occur. A more complete picture of communication problems requires understanding how communication usually works in routine operations. A sample of routine pilot-controller communication in the TRACON environment is described. After describing several dimensions of routine communication, three kinds of communication problems are treated: inaccuracies such as incorrect readbacks, procedural deviations such as missing callsigns and readbacks, and nonroutine transactions where pilot and controller must deal with misunderstandings or other communication problems. Preliminary results suggest these problems are not frequent events in daily operations. However, analysis of the problems that do occur suggest some factors that may cause them.

In the absence of national screening requirements, physicians have been vulnerable to lawsuits following sudden cardiac deaths in athletes. The American Heart Association recently recommended routine cardiovascular screening for athletes. The article suggests that it is time for mandatory, national standardized cardiovascular screening for…

A number of terms (e.g., toxic chemicals,'' toxic pollutants,'' toxic waste,'' and similar nomenclature) refer to substances that are subject to regulation under one or more federal environmental laws. State laws and regulations also provide additional, similar, or identical terminology that may be confused with the federally defined terms. Many of these terms appear synonymous, and it is easy to use them interchangeably. However, in a regulatory context, inappropriate use of narrowly defined terms can lead to confusion about the substances referred to, the statutory provisions that may apply, and the regulatory requirements for compliance under the applicable federal statues. This information Brief provides regulatory definitions, a brief discussion of compliance requirements, and reference for the precise terminology that should be used when referring to toxic'' substances regulated under federal environmental laws. A companion CERCLA Information Brief (EH-231-003/0191) addresses hazardous'' nomenclature.

Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The major toxic side-effects of antimonials as a result of therapy are cardiotoxicity (~9% of patients) and pancreatitis, which is seen commonly in HIV and visceral leishmaniasis co-infections. Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically. PMID:21318007

An ANSYS finite-element code routine to check for duplicated elements within the volume of a three-dimensional (3D) finite-element mesh was developed. The routine developed is used for checking floating elements within a mesh, identically duplicated elements, and intersecting elements with a common face. A space shuttle main engine alternate turbopump development high pressure oxidizer turbopump finite-element model check using the developed subroutine is discussed. Finally, recommendations are provided for duplicate element checking of 3D finite-element models.

The Circle Spline routine is currently being used for generating both two and three dimensional spline curves. It was developed for use in ESCHER, a mesh generating routine written to provide a computationally simple and efficient method for building meshes along curved surfaces. Circle Spline is a parametric linear blending spline. Because many computerized machining operations involve circular shapes, the Circle Spline is well suited for both the design and manufacturing processes and shows promise as an alternative to the spline methods currently supported by the Initial Graphics Specification (IGES).

This document provides the Environmental Restorations Contractor (ERC) and the Project Hanford Management Contractor (PHMC) a schedule in accordance with the HNF-PRO-454, Inactive Waste Sites` HNF-PRO-455, Solid Waste 3 Management4 and BHI-EE-02, Environmental Requirements, of monitoring and sampling, routines for the near-facility environmental monitoring program during calendar year (CY) 1998. Every attempt will be made to consistently follow this schedule; any deviation from this schedule will be documented by an internal memorandum (DSI) explaining the reason for the deviation. The DSI will be issued by the scheduled performing organization and directed to Environmental Monitoring and Investigations. The survey frequencies for particular sites are determined by the technical judgment of Environmental Monitoring and investigations and may depend on the site history, radiological status, use, and general conditions. Additional surveys may be requested at irregular frequencies if conditions warrant. All radioactive wastes sites are scheduled to be surveyed at least annually. Any newly discovered wastes sites not documented by this schedule will be included in the revised schedule for CY 1999. The outside perimeter road surveys of 200 East and West Area and the rail survey from the 300 Area to Columbia Center will be performed in the year 2000 per agreement with Department of Energy, Richland Field Office. This schedule does not discuss staffing needs, nor does it list the monitoring equipment to be used in completing specific routines. Personnel performing routines to meet this schedule shall communicate any need for 1332 assistance in completing these routines to Radiological Control management and Environmental Monitoring and Investigations. After each routine survey is completed, a copy of the survey record, maps, and data sheets will be forwarded to Environmental Monitoring and Investigations. These routine surveys will not be considered complete until this

Attempts to modify gravity in the infrared typically require a screening mechanism to ensure consistency with local tests of gravity. These screening mechanisms fit into three broad classes; we investigate theories which are capable of exhibiting more than one type of screening. Specifically, we focus on a simple model which exhibits both Vainshtein and kinetic screening. We point out that due to the two characteristic length scales in the problem, the type of screening that dominates depends on the mass of the sourcing object, allowing for different phenomenology at different scales. We consider embedding this double screening phenomenology in a broader cosmological scenario and show that the simplest examples that exhibit double screening are radiatively stable.

Homework appears to be positively associated with better student outcomes. Although some researchers have explored the connection between time spent on homework and minority student achievement, few have examined the homework routines of Latino youth. Interviews with Latino high school students show that they have some difficulty completing daily…

Individuals who are beyond the age of 85 have to confront the decrements of aging that are commonly recognized. This study examined the daily routine of the oldest old through interviews. Subjects were asked about the logistics of their daily lives, what they liked best to do, what they didn't like to do, what made a day good for them, and what…

The Modular Thermal Analyzer Routine (MOTAR) is a general thermal analysis routine with strong capabilities for performing thermal analysis of systems containing flowing fluids, fluid system controls (valves, heat exchangers, etc.), life support systems, and thermal radiation situations. Its modular organization permits the analysis of a very wide range of thermal problems for simple problems containing a few conduction nodes to those containing complicated flow and radiation analysis with each problem type being analyzed with peak computational efficiency and maximum ease of use. The organization and programming methods applied to MOTAR achieved a high degree of computer utilization efficiency in terms of computer execution time and storage space required for a given problem. The computer time required to perform a given problem on MOTAR is approximately 40 to 50 percent that required for the currently existing widely used routines. The computer storage requirement for MOTAR is approximately 25 percent more than the most commonly used routines for the most simple problems but the data storage techniques for the more complicated options should save a considerable amount of space.

We report two experiments in which errors and interaction latencies were recorded during routinization of hierarchically structured computer-based tasks. Experiment 1 demonstrates that action selection is slowed at subtask transitions, especially when selecting lower frequency actions. This frequency effect is compounded by concurrent performance…

Background: Academic procrastination, the tendency to postpone learning activities, is regarded as a consequence of postmodern values that are prominent in post-industrialized societies. When students strive for leisure goals and have no structured routines for academic tasks, delaying strenuous learning activities becomes probable. Aims: The…

Intended for use in conjunction with videos illustrating key concepts and caregiving techniques, this guide focuses on how the daily routines of caring for infants and toddlers can become opportunities for promoting the child's learning and development and for deepening the relationship between child and caregiver. Special attention is given to…

libvaxdata provides a collection of routines for converting numeric data-integer and floating-point-to and from the formats used on a Digital Equipment Corporation1 (DEC) VAX 32-bit minicomputer (Brunner, 1991). Since the VAX numeric data formats are inherited from those used on a DEC PDP-11 16-bit minicomputer, these routines can be used to convert PDP-11 data as well. VAX numeric data formats are also the default data formats used on DEC Alpha 64-bit minicomputers running OpenVMS The libvaxdata routines are callable from Fortran or C. They require that the caller use two's-complement format for integer data and IEEE 754 format (ANSI/IEEE, 1985) for floating-point data. They also require that the 'natural' size of a C int type (integer) is 32 bits. That is the case for most modern 32-bit and 64-bit computer systems. Nevertheless, you may wish to consult the Fortran or C compiler documentation on your system to be sure. Some Fortran compilers support conversion of VAX numeric data on-the-fly when reading or writing unformatted files, either as a compiler option or a run-time I/O option. This feature may be easier to use than the libvaxdata routines. Consult the Fortran compiler documentation on your system to determine if this alternative is available to you. 1Later Compaq Computer Corporation, now Hewlett-Packard Company

MEETING REPORT The successful completion of the first year of routine science operations of ESA's Herschel Space Observatory was marked by a Specialist Discussion Meeting of the RAS held in January 2011. A few of the early science highlights from the mission were presented. Derek Ward-Thompson and David Clements summarize.

Cardiovascular diseases (CVD) are the leading causes of death among Mexican American adults living in the United States. Using data from a modified Behavioral Risk Factor Surveillance Survey and guided by the Anderson Model, this study examined the effect of nativity on CVD screening practices among 423 Mexican American adults living in Chicago. Dependent variables included having had a blood pressure and cholesterol screening and a routine check up in the past 2 years. Multivariate analyses were used to control for sociodemographic factors, while accounting for complex sampling design. Compared to those born in Mexico, US-born Mexican Americans had significantly greater odds of obtaining blood pressure (OR=5.61), and cholesterol screenings (OR=1.60) and having a routine checkup (OR=2.69) in the past 2 years. Health professionals with an agenda to increase screenings for CVD risk factors among Mexican Americans living in northern cities should understand the impact of nativity on screening practices.

Background The prevalence and detrimental health effects of intimate partner violence have resulted in international discussions and recommendations that health care professionals should screen women for intimate partner violence during general and antenatal health care visits. Due to the lack of discussion on routine or case-based inquiry for intimate partner violence during antenatal care in Germany, this study seeks to explore its acceptability among pregnant German women. Methods A mixed methods approach was used, utilizing a self-administered survey on the acceptability of routine or case-based inquiry for intimate partner violence in a university hospital’s maternity ward in Munich and in-depth interviews with seven women who experienced violence during pregnancy. Results Of the 401 women who participated in the survey, 92 percent were in favor of routine or case-based inquiry for intimate partner violence during antenatal care. Acceptance of routine or case-based inquiry for intimate partner violence during antenatal care was significantly associated with women’s experiences of child sexual abuse, being young, less educated, single or divorced and smoking during pregnancy. Open-ended survey questions and in-depth interviews stressed adequate training for screening, sufficient time and provision of referral information as important conditions for routine or case-based inquiry for intimate partner violence. Conclusions Women in this study showed an overwhelming support for routine or case-based screening for intimate partner violence in antenatal care in Germany. Until adequate training is in place to allow providers to inquire for intimate partner violence in a professional manner, this study recommends that health care providers are made aware of the prevalence and health consequences of violence during pregnancy. PMID:23531127

Asthmatic patients who undergo outpatient anesthesia are typically prescribed one or more drugs for treatment. Some of these agents have narrow therapeutic ranges and are associated with potentially serious adverse reactions, toxic effects, or drug interactions. Various clinical signs of toxicity may be first uncovered during routine monitoring of an office anesthetic. The case reported here demonstrates the need for proper understanding of the asthmatic patient's medical history and an appreciation for the medications used to control the disease. A sudden cardiovascular event possibly related to drug toxicity is witnessed and treated in an asthmatic patient during intravenous sedation. A possible drug interaction with a non-asthmatic medication taken concomitantly by the patient is implicated and discussed. In addition to the case report, the broad classification of drugs employed for bronchial asthma and their effects is reviewed. PMID:10323129

Asthmatic patients who undergo outpatient anesthesia are typically prescribed one or more drugs for treatment. Some of these agents have narrow therapeutic ranges and are associated with potentially serious adverse reactions, toxic effects, or drug interactions. Various clinical signs of toxicity may be first uncovered during routine monitoring of an office anesthetic. The case reported here demonstrates the need for proper understanding of the asthmatic patient's medical history and an appreciation for the medications used to control the disease. A sudden cardiovascular event possibly related to drug toxicity is witnessed and treated in an asthmatic patient during intravenous sedation. A possible drug interaction with a non-asthmatic medication taken concomitantly by the patient is implicated and discussed. In addition to the case report, the broad classification of drugs employed for bronchial asthma and their effects is reviewed.

Less than 5% of colorectal adenomas will become malignant, but we do not have sufficient knowledge about their natural course to target removal of these 5% only. Thus, 95% of polypectomies are a waste of time exposing patients to a small risk of complications. Recently, a new type of polyps, sessile serrated polyps, has attracted attention. Previously considered innocuous, they are now found to have molecular similarities to cancer and some guidelines recommend to have them removed. These lesions are often flat, covered by mucous, not easily seen and situated in the proximal colon where the bowel wall is thinner. Thus, polypectomy carries a higher risk of perforation than predominantly left-sided, stalked adenomas - and we do not know what is gained in terms of cancer prevention. Screening is a neat balance between harms and benefit for presumptively healthy participants not interested in risk exposure to obtain confirmation of being healthy. The situation is quite different for patient worried about symptom. Thus, the standards set for evidence-based practice may be higher for screening than for routine clinics - a mechanism which may benefit patients in the long run.

Current immunotoxicity testing guidance for drugs, high production volume chemicals and pesticides specifies the use of animal models that measure immune function or evaluation of general indicators of immune system health generated in routinetoxicity testing. The assays are r...

Current immunotoxicity testing guidance for drugs, high production volume chemicals and pesticides specifies the use of animal models that measure immune function or evaluation of general indicators of immune system health generated in routinetoxicity testing. The assays are ...

Currently, a significant research effort is underway to apply new technologies to screen and prioritize chemicals for toxicity testing as well as to improve understanding of toxicity pathways (Dix et al. 2007, Toxicol Sci; NRC, 2007, Toxicity Testing in the 21st Century; Collins ...

Muscle tissue is highly sensitive to many substances. Early recognition of toxic myopathies is important, as they potentially are reversible on removal of the offending drug or toxin, with greater likelihood of complete resolution the sooner this is achieved. Clinical features range from mild muscle pain and cramps to severe weakness with rhabdomyolysis, renal failure, and even death. The pathogenic bases can be multifactorial. This article reviews some of the common toxic myopathies and their clinical presentation, histopathologic features and possible underlying cellular mechanisms. PMID:25037083

The controversial recent recommendation by the United States Preventive Services Task Force (USPSTF) against prostate-specific antigen (PSA) screening for early-stage prostate cancer has caused much debate. Whereas USPSTF recommendations against routinescreening mammography in younger women resulted in fierce public outcry and eventual alteration in the language of the recommendation, the same public and political response has not been seen with PSA screening for prostate cancer. It is of paramount importance to ensure improved efficiency and transparency of the USPSTF recommendation process, and resolution of concerns with the current USPSTF recommendation against PSA screening for all ages.

This document provides Health Physics (HP) a schedule in accordance with the Environmental Compliance Manual, WHC-CM-7-5, of monitoring and sampling routines for the Operational Environmental Monitoring (OEM) Program during calendar year (CY) 1994. The survey frequencies for particular sites are determined by the technical judgment of EES and may depend on the site history, radiological status, use, and general conditions. Additional surveys may be requested at irregular frequencies if conditions warrant. All radioactive waste sites are scheduled to be surveyed annually at a minimum. Any newly discovered waste sites not documented by this schedule will be included in the revised schedule for CY 1995. This schedule does not discuss the manpower needs nor does it list the monitoring equipment to be used in completing specific routines.

Cholangiography done routinely during operation was found valuable for detection of stones in the bile ducts. Operation for stone not seen in the operative cholangiogram was seldom necessary. When no stone is demonstrated, it seems proper to spare the patient the additional trauma of common duct exploration. ImagesFigure 1 (Case 1).Figure 2 (Case 1).Figure 3 (Case 2).Figure 4 (Case 3).Figure 5 (Case 5).Figure 6 (Case 6). PMID:13651956

What is disclosed is a novel toxic waste remediation system designed to provide on-site destruction of a wide variety of hazardous organic volatile hydrocarbons, including but not limited to halogenated and aromatic hydrocarbons in the vapor phase. This invention utilizes a detoxification plenum and radiation treatment which transforms hazardous organic compounds into non-hazardous substances.

This paper presents the results of interlaboratory toxicity tests on sediment toxicity methods for use in routine testing and this data has been presented in an EPA report and this is a summary of that data.

Abstract OBJECTIVE To provide a primer for primary care professionals who are increasingly called upon to discuss the growing number of genetic screening services available and to help patients make informed decisions about whether to participate in genetic screening, how to interpret results, and which interventions are most appropriate. QUALITY OF EVIDENCE As part of a larger research program, a wide literature relating to genetic screening was reviewed. PubMed and Internet searches were conducted using broad search terms. Effort was also made to identify the gray literature. MAIN MESSAGE Genetic screening is a type of public health program that is systematically offered to a specified population of asymptomatic individuals with the aim of providing those identified as high risk with prevention, early treatment, or reproductive options. Ensuring an added benefit from screening, as compared with standard clinical care, and preventing unintended harms, such as undue anxiety or stigmatization, depends on the design and implementation of screening programs, including the recruitment methods, education and counseling provided, timing of screening, predictive value of tests, interventions available, and presence of oversight mechanisms and safeguards. There is therefore growing apprehension that economic interests might lead to a market-driven approach to introducing and expanding screening before program effectiveness, acceptability, and feasibility have been demonstrated. As with any medical intervention, there is a moral imperative for genetic screening to do more good than harm, not only from the perspective of individuals and families, but also for the target population and society as a whole. CONCLUSION Primary care professionals have an important role to play in helping their patients navigate the rapidly changing terrain of genetic screening services by informing them about the benefits and risks of new genetic and genomic technologies and empowering them to

The early identification of toxic paraquat (PQ) poisoning in patients is critical to ensure timely and accurate prognosis. Although plasma PQ concentration has been reported as a clinical indicator of PQ poisoning, it is not commonly applied in practice due to the inconvenient necessary instruments and operation. In this study, we explored the use of blood routine indexes to identify the degree of PQ toxicity and/or diagnose PQ poisoning in patients via machine learning approach. Specifically, we developed a method based on support vector machine combined with the feature selection technique to accurately predict PQ poisoning risk status, then tested the method on 79 (42 male and 37 female; 41 living and 38 deceased) patients. The detection method was rigorously evaluated against a real-world data set to determine its accuracy, sensitivity and specificity. Feature selection was also applied to identify the factors correlated with risk status, and the results showed that there are significant differences in blood routine indexes between dead and living PQ-poisoned individuals (p-value < 0.01). Feature selection also showed that the most important correlated indexes are white blood cell and neutrophils. In conclusion, the toxicity or prognosis of PQ poisoning can be preliminarily ascertained by blood routine testing without PQ concentration data, representing an additional tool and innovative approach to assess the prognosis of PQ poisoning.

Management of cystic fibrosis (CF) is burdensome and adherence is often suboptimal. Family routines are associated with adherence and health outcomes in other disease populations. Few studies have examined routines in CF. The study's aim was to describe parent experiences developing and utilizing CF care routines. Semi-structured interviews with a convenience sample of 25 parents of children under 13 years of age with CF were analyzed using phenomenological analysis. Three domains emerged: parent experiences developing a routine, support systems facilitating maintenance of routines, and challenges with maintaining care routines. Parents found routines difficult to establish, used trial and error, encountered barriers, and found support helpful to manage care demands. Some parents chose to deviate from their routine. Providing anticipatory guidance to promote the use of care routines and strategies to manage potential challenges may facilitate use of routines and improve CF management. PMID:24838648

Pesticide mixtures are common in streams with agricultural or urban influence in the watershed. The Pesticide Toxicity Index (PTI) is a screening tool to assess potential aquatic toxicity of complex pesticide mixtures by combining measures of pesticide exposure and acute toxicity in an additive toxic-unit model. The PTI is determined separately for fish, cladocerans, and benthic invertebrates. This study expands the number of pesticides and degradates included in previous editions of the PTI from 124 to 492 pesticides and degradates, and includes two types of PTI for use in different applications, depending on study objectives. The Median-PTI was calculated from median toxicity values for individual pesticides, so is robust to outliers and is appropriate for comparing relative potential toxicity among samples, sites, or pesticides. The Sensitive-PTI uses the 5th percentile of available toxicity values, so is a more sensitive screening-level indicator of potential toxicity. PTI predictions of toxicity in environmental samples were tested using data aggregated from published field studies that measured pesticide concentrations and toxicity to Ceriodaphnia dubia in ambient stream water. C. dubia survival was reduced to ≤ 50% of controls in 44% of samples with Median-PTI values of 0.1–1, and to 0% in 96% of samples with Median-PTI values > 1. The PTI is a relative, but quantitative, indicator of potential toxicity that can be used to evaluate relationships between pesticide exposure and biological condition.

Fungicides are widely used in agriculture, and released in large amounts to the environment. Methods used for antifungal susceptibility testing are cumbersome and time-consuming. As a result, very little attention has been paid to including fungal tests in the routinescreening of pesticides and there are no reports in the literature of fungicide focussed effects directed analysis (EDA). In addition very little is known on the toxicity of fungicides to environmentally significant fungi. Here we report a rapid microplate-based resorufin fluorescence inhibition bioassay and compare it with a 24h microplate-based yeast growth inhibition bioassay using eight fungicides. The growth inhibition bioassay was sensitive, giving IC50 and IC90 values comparable to previously reported IC50 or MICs of these fungicides for Saccharomyces cerevisiae and other fungi. The resorufin fluorescence inhibition bioassay was both faster and more sensitive than the growth inhibition bioassay. Inhibitory concentrations obtained just after 30min of incubation with amphotericin B (AMB) and captan were at least a hundred fold lower than IC50s in the literature for fungi. The fluorescence bioassay showed only a small response to pyrazophos and thiabendazole but these only inhibited growth at high concentrations so this may reflect low sensitivity of S. cerevisiae to these particular fungicides. This bioassay can detect toxic effects of a range of fungicides from different chemical classes with different modes of action. It will be valuable for screening chemical libraries for fungicides and as a biomarker for detecting the effects of fungicides to non-target fungi.

A growing number of agents are known to perturb one or more of the interconnected processes of the central nervous system. At the same time, there is an increase in the incidence of neurobehavioral disorders that are confronting clinicians with baffling symptoms and presentations that seem uncommon. Fundamental to the assessment of the environmental-relatedness of the syndromes is a work and exposure history, including information different from that routinely obtained in the clinical setting. Exposure examples are described to suggest the scope of inquiry necessary to differentiate neurotoxic syndromes from nonneurotoxic illness. PMID:10745641

Toxicity testing and chemical analyses of sediment pore water have been suggested for use in sediment quality assessments and sediment toxicity identification evaluations. However, caution should be exercised in interpreting pore-water chemistry and toxicity due to inherent chemical characteristics and confounding relationships. High concentrations of alkalinity, which are typical of sediment pore waters from many regions, have been shown to be toxic to test animals. A series of tests were conducted to assess the significance of elevated alkalinity concentrations to Hyalella azteca, an amphipod commonly used for sediment and pore-water toxicity testing. Toxicity tests with 14-d old and 7-d old animals were conducted in serial dilutions of sodium bicarbonate (NaHCO3) solutions producing alkalinities ranging between 250 to 2000 mg/L as CaCO3. A sodium chloride (NaCl) toxicity test was also conducted to verify that toxicity was due to bicarbonate and not sodium. Alkalinity was toxic at concentrations frequently encountered in sediment pore water. There was also a significant difference in the toxicity of alkalinity between 14-d old and 7-d old animals. The average 96-h LC50 for alkalinity was 1212 mg/L (as CaCO3) for 14-d old animals and 662 mg/L for the younger animals. Sodium was not toxic at levels present in the NaHCO3 toxicity tests. Alkalinity should be routinely measured in pore-water toxicity tests, and interpretation of toxicity should consider alkalinity concentration and test-organism tolerance.

Cadmium is a well-known environmental pollutant with distinctly toxic effects on plants. It can displace certain essential metals from a wealth of metalloproteins, and thus disturb many normal physiological processes and cause severe developmental aberrant. The harmful effects of cadmium stress include, but are not limited to: reactive oxygen species overproduction, higher lipid hydroperoxide contents, and chloroplast structure change, which may lead to cell death. Plants have developed diverse mechanisms to alleviate environmental cadmium stress, e.g., cadmium pump and transporting cadmium into the leaf vacuoles. This mini-review focuses on the current research into understanding the cellular mechanisms of cadmium toxicity on cytoskeleton, vesicular trafficking and cell wall formation in plants. PMID:22499203

Background to the debate: The US and Canadian task forces on preventive health recently declared that there is not enough evidence to recommend for or against routine universal screening of women for domestic violence. Yet some experts argue that routine enquiry is justified. PMID:15526052

An overview of the widespread use of gases and some volatile solvents in modern society is given. The usual circumstances in which undue exposure may occur are described. The most prominent symptoms and general principles of diagnosis and treatment are given and are followed by more specific information on the commoner, more toxic materials. While acute poisonings constitute the greater part of the paper, some indication of chronic disorders arising from repeated or prolonged exposure is also given. PMID:2687827

When life needs routine, imagination, listening. Barbara is a 44 years old oncologist, married and with two children, that tells through others but also with her own words of her cancer, until death. Giuseppe is a laboratory technician, researcher, mountaineer, promoter of humanitarian initiatives Bosnia and Croatia; his lateral amyotrophic sclerosis is told by his wife, in a booklet written after his death. Their two stories are the occasions for reflecting on the importance and role of closeness, listening, dreaming, narrating in improving the quality of life and care: none of these words are included in the guidelines.

With funding from the George Mitchell Center for the Environment at the University of Maine, a team of scientists used a simple laboratory-based sediment resuspension design, and two well-established aquatic toxicology models, fathead minnows (Pimephales promelas) and zebrafish (Danio rerio), to evaluate if resuspension of Penobscot river sediment significantly elevates the toxicity of river water and to provide preliminary information on the types of chemicals likely to desorb during resuspension. The group collected sediments from two sites with known chemical contamination downstream of the Great Works and Veazie dams. The sediments were examined to determine the dynamics of PAH desorption and degradation under different resuspension frequencies. The scientists used clarified water from resuspension experiments for toxicity tests with the water-flea Ceriodaphnia dubia, and other aquatic test organisms to infer toxicity from sediments from northern California rivers. Data from the study will help ascertain whether metals and/or xenoestrogens are present in the desorption water and give insight into possible avenues of sediment remediation.

OBJECTIVE: To evaluate the extent and type of screening for cognitive impairment primary care physicians use for their elderly patients, to identify perceived barriers to screening, and to explore whether physicians would be willing to use the clock drawing test as a cognitive screening tool. DESIGN: Mailed questionnaire. SETTING: Primary care practices in the Ottawa-Carleton region. PARTICIPANTS: Family physicians and general practitioners culled from the Yellow Pages and Canadian Medical Directory; 368 of 568 questionnaires were returned for a response rate of 70%. Six respondents had fewer than 30 patients weekly and two responded too late to be included in the analysis; 360 cases were included in the analysis. MAIN OUTCOME MEASURES: Responses to 10 questions on cognitive screening and five on demographics and the nature of respondents' practices. RESULTS: About 80% of respondents reported doing at least one mental status examination during the past year. Only 24% routinelyscreened patients, although 82% believed screening was needed. Major barriers to cognitive screening were lack of time, risk of offending patients, and possible negative consequences of follow up. Clock drawing was perceived as an acceptable method of screening, if it were proven effective. CONCLUSIONS: Most primary care physicians believe cognitive screening is needed, but few routinelyscreen their elderly patients. Lack of time is the most important perceived barrier to screening. Primary care physicians are receptive to using the clock drawing test, and, because it is not time-consuming, are less likely to consider lack of time a barrier to testing. The clock test might help bridge the gap between perceived need for screening and actual screening. PMID:9356757

Context: Alcohol misuse is more common in rural areas, and rural problem drinkers are less likely to seek alcohol treatment services. Rural clinics face unique challenges to implementing routine alcohol screening and intervention. Purpose: To assess the feasibility of using the single alcohol screening question (SASQ) during routine nursing vital…

An attempt was made to measure the response to an announcement of hypertension screening at the Goddard Space Center, to compare the results to those of previous statistics. Education and patient awareness of the problem were stressed.

... health. Depending on your age, sex, and medical history, you may need to be screened for things like: Certain types of cancer High blood pressure or high cholesterol Diabetes Osteoporosis (weak bones) ...

Objectives: To assess the performance of routine syphilis screening during 5 year follow up of Ethiopian factory workers, participating in a cohort study on HIV/AIDS. Methods: Syphilis serology test results of factory workers, who each donated at least six blood samples were evaluated. Screening in 1997–8 had been performed by the Treponema pallidum particle agglutination (TPPA) assay and in 1999–2001 by the rapid plasma reagin (RPR) test. TPPA had been followed by RPR or RPR by TPPA, in case of a positive screening result. Samples of study subjects showing inconsistent sequential TPPA and/or RPR results were retested independently by three laboratory technicians. Results: A total of 540 cohort participants (8.3% HIV positive at enrolment) donated 4376 blood samples (mean 8.3 per subject). From 93 of the 176 participants with at least one positive TPPA result during follow up, 152 samples were retested by RPR and/or TPPA. Based on the revised syphilis test results, the 540 cohort participants were classified as having no (70.5%), past (20.6%), prevalent (6.9%), or incident (2.0%) syphilis. The RPR screening test was difficult to interpret and yielded 8.2% biological false positive (BFP) RPR results, or 3.2% if weak positive results were excluded. There was no correlation between HIV infection and BFP RPR reactions. Sample mix-ups were detected in 1.2%. Conclusion: Evaluation of routine syphilis screening as performed in a long term cohort study on HIV/AIDS in Ethiopia showed difficulties encountered in syphilis screening programmes such as a high percentage of BFP RPR, inconsistencies in interpretation of the RPR test, and sample mix ups. The findings stress the need to develop a syphilis screening assay that is easy to perform and interpret and to implement quality assurance programmes. PMID:15054167

The purpose of this package is to provide the scientific and engineering community with a library of programs useful for performing routine mathematical manipulations. This collection of programs will enable scientists to concentrate on their work without having to write their own routines for solving common problems, thus saving considerable amounts of time. This package contains sixteen subroutines. Each is separately documented with descriptions of the invoking subroutine call, its required parameters, and a sample test program. The functions available include: maxima, minima, and sort of vectors; factorials; random number generator (uniform or Gaussian distribution); complimentary error function; fast Fourier Transformation; Simpson's Rule integration; matrix determinate and inversion; Bessel function (J Bessel function for any order, and modified Bessel function for zero order); roots of a polynomial; roots of non-linear equation; and the solution of first order ordinary differential equations using Hamming's predictor-corrector method. There is also a subroutine for using a dot matrix printer to plot a given set of y values for a uniformly increasing x value. This package is written in FORTRAN 77 (Super Soft Small System FORTRAN compiler) for batch execution and has been implemented on the IBM PC computer series under MS-DOS with a central memory requirement of approximately 28K of 8 bit bytes for all subroutines. This program was developed in 1986.

The timing routines available on the CONVEX C220 computer system in the Structural Mechanics Division (SMD) at NASA Langley Research Center are examined. The function of the timing routines, the use of the timing routines in sequential, parallel, and vector code, and the interpretation of the results from the timing routines with respect to the CONVEX model of computing are described. The timing routines available on the SMD CONVEX fall into two groups. The first group includes standard timing routines generally available with UNIX 4.3 BSD operating systems, while the second group includes routines unique to the SMD CONVEX. The standard timing routines described in this report are /bin/csh time,/bin/time, etime, and ctime. The routines unique to the SMD CONVEX are getinfo, second, cputime, toc, and a parallel profiling package made up of palprof, palinit, and palsum.

The screening test method was used to investigate toxicity in polyethylene, polystyrene, polymethyl methacrylate, polyaryl sulfone, polyether sulfone, polyphenyl sulfone, and polyphenylene sulfide. Changing from a rising temperature program to a fixed temperature program resulted on shorter times to animal responses. This effect was attributed in part to more rapid generation of toxicants. The toxicants from the sulfur containing polymers appeared to act more rapidly than the toxicants from the other polymers. It was not known whether this effect was due primarily to difference in concentration or in the nature of the toxicants. The carbon monoxide concentration found did not account for the results observed with the sulfur containing polymers. Polyphenyl sulfone appeared to exhibit the least toxicity among the sulfur containing polymers evaluated under these test conditions.

Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed tumour diseases throughout the world. In the vast majority of cases those affected are high-risk patients with chronic viral hepatitis and/or liver cirrhosis, which means there is a clearly identifiable target group for HCC screening. With resection, transplantation, and interventional procedures for local ablation, following early diagnosis curative treatment options are available with which 5-year survival rates of over 60% can be reached. Such early diagnosis is a reality only in a minority of patients, however, and in the majority of cases the disease is already in an advanced stage at diagnosis. One of the objects of HCC screening is diagnosis in an early stage when curative treatment is still possible. Precisely this is achieved by screening, so that the proportion of patients treated with curative intent is decisively higher. There is not yet any clear evidence as to whether this leads to a lowering of the mortality of HCC. As lower mortality is the decisive indicator of success for a screening programme the benefit of HCC screening has so far been neither documented nor refuted. Nonetheless, in large regions of the world it is the practice for high-risk patients to undergo HCC screening in the form of twice-yearly ultrasound examination and determination of AFP.

This report involves a 54-year-old man who died following refractory ventricular fibrillation after ingestion of a plant in a suicide attempt. Repeated direct-current cardioversions were unsuccessful and no single anti-arrhythmic agent was effective for arrhythmia control. The routine blood toxicological screening was negative. Aconitine, the main toxin of Aconitum napellus was identified using a specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The whole blood concentration (24 microg/l) was higher than those reported in other aconitine-related deaths. The patient had found information about the life-threatening nature of such a toxic herb intake on a free medical encyclopedia online.

Pediatricians can play a key role in preventing and controlling HIV infection by promoting risk-reduction counseling and offering routine HIV testing to adolescent and young adult patients. Most sexually active youth do not feel that they are at risk of contracting HIV and have never been tested. Obtaining a sexual history and creating an atmosphere that promotes nonjudgmental risk counseling is a key component of the adolescent visit. In light of increasing numbers of people with HIV/AIDS and missed opportunities for HIV testing, the Centers for Disease Control and Prevention recommends universal and routine HIV testing for all patients seen in health care settings who are 13 to 64 years of age. There are advances in diagnostics and treatment that help support this recommendation. This policy statement reviews the epidemiologic data and recommends that routinescreening be offered to all adolescents at least once by 16 to 18 years of age in health care settings when the prevalence of HIV in the patient population is more than 0.1%. In areas of lower community HIV prevalence, routine HIV testing is encouraged for all sexually active adolescents and those with other risk factors for HIV. This statement addresses many of the real and perceived barriers that pediatricians face in promoting routine HIV testing for their patients.

Elevating ambient temperature above thermoneutrality exacerbates toxicity of most air pollutants, insecticides, and other toxic chemicals. On the other hand, safety and toxicity testing of toxicants and drugs is usually performed in mice and rats maintained at subthermoneutral te...

High-throughput screening (HTS) technologies, along with efforts to improve public access to chemical toxicity information resources and to systematize older toxicity studies, have the potential to significantly improve information gathering efforts for chemical assessments and p...

A 96-condition initial screen for protein crystallization, called MORPHEUS, has been developed at the MRC Laboratory of Molecular Biology, Cambridge, England (MRC-LMB). The concept integrates several innovative approaches, such as chemically compatible mixes of potential ligands, new buffer systems and precipitant mixes that also act as cryoprotectants. Instead of gathering a set of crystallization conditions that have already been successful, a selection of molecules frequently observed in the Protein Data Bank (PDB) to co-crystallize with proteins has been made. These have been put together in mixes of similar chemical behaviour and structure, and combined with buffers and precipitant mixes that were also derived from PDB searches, to build the screen de novo. Observations made at the MRC-LMB and many practical aspects were also taken into account when formulating the screen. The resulting screen is easy to use, comprehensive yet small, and has already yielded a list of crystallization hits using both known and novel samples. As an indicator of success, the screen has now become one of the standard screens used routinely at the MRC-LMB when searching initial crystallization conditions for biological macromolecules.

Aflibercept is a new anti-vegf drug that, unlike ranibizumab and bevacizumab blocks both vegf-A and placental growth factor. Moreover, it binds with much greater strength and affinity to human VEGF-A165 than other endogenous vegf receptors, conferring it with a more extended effect and allowing a lower frequency of intravitreal injections. This facilitates the adoption of fixed treatment regimens other than monthly or individual regimens such as "treat and extend". Aflibercept is indicated for the treatment of neovascular (exudative) age-related macular degeneration (ARMD), visual alteration due to macular edema secondary to central retinal vein occlusion (CRVO) and visual alteration due to diabetic macular edema (DME). The present article reviews the management of aflibercept in routine clinical practice, based on the specifications of its new core data sheet, which includes all the therapeutic indications in which its use has been approved and evaluating the distinct alternatives and treatment regimens after the initial loading doses.

Bulk sediment toxicity tests are routinely used to assess the level and extent of contamination in natural sediments. While reliable, these tests can be resource intensive, requiring significant outlays of time and materials. The purpose of this study was to compare the results ...

reporting period, we have completed screening for microbial growth and nearly finished the proposed sequencing. Sequencing would have been completed... microbial strains that produce industrially relevant biochemicals routine. Recent synthetic biology techniques can make billions of variant cells...industrially relevant biomolecules) are identified using microbial growth assays, sequencing, and quantitative PCR (qPCR). To demonstrate that such

Many work processes take place through routines, or recurrent patterns of action. These activities involve individuals from several occupations working across spatial, temporal, and organizational boundaries. Crossing these professional, temporal and spatial boundaries has unique challenges which can lead to coordination failures. In these…

Roundworm infestation is common in tropical climate population with a low socioeconomic status. We describe a case of a young male with polytrauma accident who presented with small bowel dysfunction with a high gastric residual volume during enteral feeding. While searching the etiology, the intensivist performed bedside abdominal ultrasound (USG) as a part of whole body USG screening along with clinical examination using different frequency probes to examine bowel movement and ultimately found ascariasis to be the cause. This case report will boost up the wide use of bedside USG by critical care physicians in their patient workup. PMID:26430346

Hepatotoxicity is the most common organ injury due to occupational and environmental exposures to industrial chemicals. A wide range of liver pathologies ranging from necrosis to cancer have been observed following chemical exposures both in humans and in animal models. Toxicant-associated fatty liver disease (TAFLD) is a recently named form of liver injury pathologically similar to alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). Toxicant-associated steatohepatitis (TASH) is a more severe form of TAFLD characterized by hepatic steatosis, inflammatory infiltrate, and in some cases, fibrosis. While subjects with TASH have exposures to industrial chemicals, such as vinyl chloride, they do not have traditional risk factors for fatty liver such as significant alcohol consumption or obesity. Conventional biomarkers of hepatotoxicity including serum alanine aminotransferase activity may be normal in TASH, making screening problematic. This article examines selected chemical exposures associated with TAFLD in human subjects or animal models and concisely reviews the closely related NAFLD and ALD. PMID:23262638

The words "routine" and "ritual" are sometimes used interchangeably. Yet there are some important differences. Routines are repeated, predictable events that provide a foundation for the daily tasks in a child's life. Teachers can create a predictable routine in early childhood settings for infants and toddlers, and they can individualize those…

Articulators have been widely used by clinicians of dentistry. But routine articulator mounting is still controversial in orthodontics. Orthodontists oriented by gnathology approve routine articulator mounting while nongnathologic orthodontists disapprove it. This article reviews the thoughts of orthodontist that they agree or disagree with routine articulator mounting based on the considerations of biting, temporomandibular disorder (TMD), periodontitis, and so on.

In early childhood settings, children spend over 50 percent of their time on handwashing, dressing, napping, and other routines and transitions. "Routines and Transitions" is a guide to help turn these routine daily activities into learning experiences. By using transitions wisely, providers not only help children develop skills, but also run a…

The popular parenting literature places great importance on the role of routines in children's lives. Empirical research on family routines, however, is limited. This study examined correlates of family routines in a Head Start population in order to better understand their significance in the lives of families. Weak correlations were found…

A review of toxic materials in the environment explores the evolution of public awareness of the problem, public and governmental reaction, the effort to establish standards of safe levels and danger thresholds, and the struggle to implement and enforce environmental policy. Separate chapters deal with environmental premises and scientific realities, the DDT debate and birth of environmentalism, the disaster of Love Canal, pesticides, PCBs, PBBs, formaldehyde, dioxin, air pollution, water pollution, nuclear energy and radioactive materials, acid rain, and the status of American health. The book concludes with a chapter on the need for scientific research and hard evidence to either prove or disprove the pessimism of those who warn of a threat to human health and survival.

Hearing levels are threatened by modern life--headsets for music, rock concerts, traffic noises, etc. It is crucial we know our hearing levels so that we can draw attention to potential problems. This exercise requires that students receive a hearing screening for their benefit as well as for making the connection of hearing to listening.

A liquid chromatography with tandem mass spectrometry method was developed for the simultaneous screening of 34 drugs and poisons in forensic cases. Blood (0.5 mL, diluted 1:1 with water) or 1.0 mL of urine was purified by solid-phase extraction. Gastric contents (diluted 1:1 with water) were treated with acetonitrile, centrifuged, and supernatant injected. Detection was achieved using a Waters Alliance 2695/Quattro Premier XE liquid chromatography tandem mass spectrometry system equipped with electrospray ionization, operated in the multiple reaction monitoring modes. The method was validated for accuracy, precision, linearity, and recovery. The absolute recovery of drugs and toxic compounds in blood was greater than 51% with the limit of detection in the range of 0.02-20 ng/mL. The absolute recovery of drugs and toxic compounds in urine was greater than 61% with limit of detection in the range of 0.01-10 ng/mL. The matrix effect of drugs and toxic compounds in urine was 65-117% and 67-121% in blood. The limit of detection of drugs and toxic compounds in gastric content samples were in the range of 0.05-20 ng/mL. This method was applied to the routine analysis of drugs and toxic compounds in postmortem blood, urine, and gastric content samples. The method was applied to actual forensic cases with examples given.

The presentation will provide an overview of the procedures used in deriving mammalian and avian wildlife toxicity reference values to be used in development of ecological soil screening levels (Eco-SSLs).

The Toxicity Estimation Software Tool (T.E.S.T.) has been developed to estimate toxicological values for aquatic and mammalian species considering acute and chronic endpoints for screening purposes within TSCA and REACH programs.

The modern graphics processing unit (GPU) found in many standard personal computers is a highly parallel math processor capable of nearly 1 TFLOPS peak throughput at a cost similar to a high-end CPU and an excellent FLOPS/watt ratio. High-level linear algebra operations are computationally intense, often requiring O(N3) operations and would seem a natural fit for the processing power of the GPU. Our work is on CULA, a GPU accelerated implementation of linear algebra routines. We present results from factorizations such as LU decomposition, singular value decomposition and QR decomposition along with applications like system solution and least squares. The GPU execution model featured by NVIDIA GPUs based on CUDA demands very strong parallelism, requiring between hundreds and thousands of simultaneous operations to achieve high performance. Some constructs from linear algebra map extremely well to the GPU and others map poorly. CPUs, on the other hand, do well at smaller order parallelism and perform acceptably during low-parallelism code segments. Our work addresses this via hybrid a processing model, in which the CPU and GPU work simultaneously to produce results. In many cases, this is accomplished by allowing each platform to do the work it performs most naturally.

Up to 13% of patients with epilepsy have moderate or severe sleep-disordered breathing, in particular obstructive sleep apnea (OSA), a disorder associated with reduced quality of life, worsened seizure control, and increased cardiovascular morbidity and mortality. Combining video-EEG monitoring with polysomnography (VPSG) provides the opportunity to diagnose clinically significant OSA as well as relate the occurrence of seizures and the epilepsy diagnosis to the presence and severity of sleep-disordered breathing. We have established routine VPSG in our inpatient video-EEG monitoring unit and present our findings in 87 patients. Clinically significant sleep-disordered breathing was diagnosed in 19 of 87 (22%) patients. Patients with psychogenic non-epileptic seizures (PNES) had poorer sleep quality compared to patients with epilepsy and those with neither diagnosis, whereas the prevalence of clinically significant sleep-disordered breathing in patients with PNES (29%) did not differ significantly compared to patients with epilepsy (21%) and those with neither diagnosis (22%). The differences in sleep quality are not explained by differences in body mass index (BMI) or anti-epileptic drug (AED) effects.

Swarna - Vanga, an Ayurvedic preparation, is used in the treatment mainly of Pramehas (genitor urinary and metabolic disorders), Sveta Pradara (Leucorrhoea), Kasa - Swasa (Respiratory disorders), etc. The drug contains tin and sulphur as major components along with traces of mercury, iron and aluminum. According to modern point of view certain metals have been claimed toxic to both human and animal. Since Svarna - Vanga contains these metals, it is essential to screen out its toxic effect, if any, although it is claimed in Ayurveda that when a metal is processed as prescribed, it become non - toxic or the least toxic. Considering the above facts, an animal experiment was carried out for short duration (14 days) to screen the toxic effects of Svarna - Vanga (SV) in increasing doses of the drug starting from the maximum therapeutic dose (12.5 mg / 100 gm b.wt / day). The drug was found to have no toxic effects in tissues of the animal at doses of 12.5 mg and 25 mg / 100 gm b.wt. / day. Fine fatty vacuolization in liver and focal superficial mucosal degeneration and necrosis of small intestine confined to one animal each at dose of 50 mg / 100gm b.wt. and 100 mg/ 100 gm. b.wt. / day were observed. Our study indicates that the drug has no toxic effect on tissues at therapeutic dose.

The assessment of systemic lupus erythematosus (SLE) patients in routine clinical practice is mainly based on the experience of the treating physician. This carries the risk of unwanted variability. Variability may have an impact on the quality of care offered to SLE patients, thereby affecting outcomes. Recommendations represent systematically developed statements to help practitioners in reducing variability. However, major difficulties arise in the application of recommendations into clinical practice. In this respect, the use of quality indicators may raise the awareness among rheumatologists regarding potential deficiencies in services and improve the quality of health care. The aim of this study was to develop a set of quality indicators (QI) for SLE by translating into QIs the recently developed EULAR Recommendations for monitoring SLE patients in routine clinical practice and observational studies. Eleven QIs have been developed referring to the use of validated activity and damage indices in routine clinical practice, general evaluation of drug toxicity, evaluation of comorbidities, eye evaluation, laboratory assessment, evaluation of the presence of chronic viral infections, documentation of vaccination and of antibody testing at baseline. A disease specific set of quality assessment tools should help physicians deliver high quality of care across populations. Routine updates will be needed. PMID:21224016

BRIDGES is a bioanalytical tool that combines passive sampling with the embryonic zebrafish developmental toxicity bioassay to provide a quantitative measure of the toxicity of bioavailable complex mixtures. Passive sampling devices (PSDs), which sequester and concentrate bioavailable organic contaminants from the environment, were deployed in the Willamette and Columbia Rivers within and outside of the Portland Harbor Superfund site in Portland, Oregon. Six sampling events were conducted in the summer and fall of 2009 and 2010. PSD extracts were analyzed for polycyclic aromatic hydrocarbon (PAH) compounds and screened for 1201 chemicals of concern using deconvolution reporting software. The developmental toxicity of the extracts was analyzed using the embryonic zebrafish bioassay. BRIDGES provided site-specific, temporally resolved information about environmental contaminant mixtures and their toxicity. Multivariate modeling approaches were applied to paired chemical and toxic effects data sets to help unravel chemistry-toxicity associations. Modeling demonstrated a significant correlation between PAH concentrations and the toxicity of the samples and identified a subset of PAH analytes that were the most highly correlated with observed toxicity. Although this research highlights the complexity of discerning specific bioactive compounds in complex mixtures, it demonstrates methods for associating toxic effects with chemical characteristics of environmental samples. PMID:23001962

The Visi Screen OSS-C, marketed by Vision Research Corporation, incorporates image processing technology originally developed by Marshall Space Flight Center. Its advantage in eye screening is speed. Because it requires no response from a subject, it can be used to detect eye problems in very young children. An electronic flash from a 35 millimeter camera sends light into a child's eyes, which is reflected back to the camera lens. The photorefractor then analyzes the retinal reflexes generated and produces an image of the child's eyes, which enables a trained observer to identify any defects. The device is used by pediatricians, day care centers and civic organizations that concentrate on children with special needs.

All WFPC, FOC, FOS, GHRS, HSP observations taken by the Hubble Space Telescope are automatically processed by the Routine Science Data Processing (RSDP) ``pipeline'' at STScI, under the Post Observation Data Processing System (PODPS) branch. Over 36,000 readouts have been processed since launch, 97% of these within two days of execution. Packetized science data enter the pipeline after telemetry bit-error correction at the Data Capture Facility, GSFC. Software sorts the data by observation, inserts fill packets as needed, and examines the data structure for errors. If none, the Edited Information Set is converted into a generic (waivered FITS) format. If repair is required (1-2% of observations), tested procedures are used to modify erroneous bits or keywords. The observation is then calibrated, and a film file or laser plot is generated. The HST instrument teams supply all information for calibration performed by RSDP. As calibration evolves, PODPS updates the flat fields and other files and tables for subsequent pipeline processing. Also, the observer may recalibrate the data with STSDAS tools. PODPS staff astronomers, using STSDAS IRAF tasks and SAOimage, evaluate the quality of each observation and provide keywords such as `OK' or `UNDEREXP' plus informative comments to the archive catalog. Comments often include information from the Observation Support Branch (OSS) regarding guide star acquisition success, centering slews, high jitter, etc. Observation data (in packetized, reformatted, and calibrated form) and their comments are placed in the HST science and ancillary optical disk archives (now by DMF, to be superseded by DADS). FITS tapes containing both uncalibrated and calibrated files are written for the GO by the Data Systems Operations Branch (DSOB), and prints or plots plus OSS and PODPS comments are mailed with the tapes. The authors are staff members of the Space Telescope Science Institute.

Macrocytosis, a condition in which erythrocytes are larger than normal manifests as an increase in mean corpuscular volume (MCV) more than 100 fl. The aim of this study was to identify the underlying causes of macrocytosis, detected in routine hemograms and to evaluate the hematological features in different etiologies. This study included 178 adult patients whose detailed medical history was recorded, and Vitamin B12 assay, folate assay, thyroid function tests, liver function tests, complete blood counts and peripheral smear evaluation was performed. Alcoholism was identified as the etiological factor in 65 cases (36.5%), Vitamin B12 deficiency in 43 cases (24.1%) and drug related in 23 cases (12.9%). These three conditions accounted for 73.6% of macrocytosis. Other causes identified were folate deficiency, liver disease, Myelodysplastic syndrome, chronic renal failure and Aplastic anemia. In 41 cases, the cause of macrocytosis could not be explained. Anemia was observed in 95 cases (53.3%) being most common in Vitamin B12 deficiency. 9 cases (20.9%) of Vitamin B12 deficiency presented with isolated macrocytosis without anemia. It was observed that mean hemoglobin was lower and red cell distribution width (RDW) higher in megaloblastic conditions. Peripheral smear revealed hypersegmented neutrophils in 86% and macro-ovalocytes in 72% of the megaloblastic cases. Complete medical history, red cell parameters and peripheral blood smear are simple, inexpensive tools which assist in identifying the underlying cause of macrocytosis, particularly in resource limited settings. Macrocytosis needs to be evaluated even in the absence of anemia, as it may be the first clue to an underlying pathology.

Presently, there are few legal restrictions on the use of medical screening of workers. The Occupational Safety and Health Act (OSH Act) requires that certain medical tests be performed when workers will be exposed to specific toxic substances. The OSH Act does not, however, prohibit the use of any medical screening measure nor does it indicate what actions an employer may or may not take as a result of such information. (A notable exception is the medical removal provision of the Lead Standard). This paper discusses that protection afforded under Title VII of the Civil Rights Act of 1964, the Age Discrimination in Employment Act, and the Rehabilitation Act of 1973. This paper will demonstrate that the law has, in general, failed to take into account the discriminatory aspects of medical screening.

Eighteen samples of aircraft seat materials were evaluated for relative toxicity using the USF/NASA toxicityscreening test method. Nine samples were upholstery fabrics and nine samples were cushioning foams. Under these particular conditions of test, the aromatic phenolic and aromatic polyamide fabrics exhibited less toxicity than the samples of wool and wool/nylon fabrics, and the samples of neoprene foams exhibited less toxicity than the samples of polyurethane foams. These relative toxicity rankings were obtained using both apparent lethal concentration for 50 percent of the test animals (ALC50), and time to death (Td) at a fixed weight of material.

There is a kind of transitional phenomenon found among certain borderline patients which is quite distinct from Winnicott's transitional object. These are patients who are preoccupied with maintaining proper physical distance from their objects, in order to regulate anxieties about isolation on the one hand, and identity-annihilating closeness on the other. Since they believe the activity of looking to be intrusive and devouring, hence dangerous, transparent screens are interposed between self and other, and serve as protective barriers. These screens function intrapsychically as well, to split off or hide those aspects of the self felt to be unacceptable. The analyst may witness the failure of the screen in several ways: it may create too great a distance, isolating the individual and keeping him from life; it may become contaminated by projections and turn into a persecutor, or trap the individual, a state of intolerable claustrophobia; most dramatically, it may suddenly shatter. The latter is associated with psychosis and death, and its appearance may be a harbinger of suicide.

High-throughput and high-content screening (HTS-HCS) studies are providing a rich source of data that can be applied to in vitro profiling of chemical compounds for biological activity and potential toxicity. EPA’s ToxCast™ project, and the broader Tox21 consortium, in addition t...

As more has been learned about the benefits and harms of prostate-specific antigen (PSA) screening, organizations have begun to recommend against routinescreening. Screening is a personal decision that, according to most experts, a man should make in consultation with his doctor, after he has been informed in detail about the potential benefits and harms. |

Determines the frequency of presumptive iron deficiency and lead toxicity in 198 Utah migrant children, aged 9-72 months. There were no confirmed cases of lead toxicity. Thirteen percent of all children tested, and 30 percent of those aged 9-23 months, were iron deficient. Hematocrit determination is an insensitive screen for iron deficiency.…

Background Iron depletion/deficiency in blood donors frequently results in deferrals for low hemoglobin, yet blood centers remain reluctant to dispense iron replacement therapy to donors. Study Design and Methods During a 39-month period, 1236 blood donors deferred for hemoglobin <12.5 g/dL and 400 non-deferred control donors underwent health history screening and laboratory testing (CBC, iron studies). Iron depletion and deficiency were defined as ferritin of 9–19 mcg/L and <9 mcg/L in females and 18–29 mcg/L and <18 mcg/L in males. Deferred donors and iron-deficient control donors were given a 60-pack of ferrous sulfate 325 mg tablets, and instructed to take one tablet daily. Another 60-pack was dispensed at all subsequent visits. Results In the low hemoglobin group, 30% and 23% of females and 8% and 53% of males had iron depletion or deficiency, respectively, compared with 29% and 10% of females and 18% and 21% of males in the control group. Iron depleted/deficient donors taking iron showed normalization of iron-related laboratory parameters, even as they continued to donate. Compliance with oral iron was 68%. Adverse gastrointestinal effects occurred in 21% of donors. The study identified 13 donors with serious medical conditions, including eight with GI bleeding. No donors had malignancies or hemochromatosis. Conclusion Iron depletion or deficiency was found in 53% of female and 61% of male low hemoglobin donors, and in 39% of female and male control donors. Routine administration of iron replacement therapy is safe, effective, and prevents the development of iron depletion/deficiency in blood donors. PMID:22211316

The focus of this project is to recreate and analyze the effectiveness of the original Apollo Starter Routine (ASR) which was used to generate the state vector of the Apollo spacecraft based on a series of radiometric observations. The original Apollo navigation software is unavailable in a modern programming language and the original coding has not been preserved. This necessitates its recreation using the original software documentation. Space Shuttle navigation software does not typically use the ASR or an algorithm like it since the Shuttle s state vector is easily deduced from GPS information or other sources. However, this tactic will be ineffective when trying to determine the state vector of a craft approaching, departing or in orbit around the Moon since the GPS network faces the surface of the Earth, not outer space. The recreation of the ASR from the original documentation is therefore vital as a simulation baseline for the navigation software under development for the Constellation program. The algorithms that make up the ASR will be extracted from the original documentation and adapted for and then implemented in a modern programming language; the majority of it will be coded in Matlab. The ASR s effectiveness will then be tested using simulated tracking data. The ability of the ASR to handle realistically noisy data and the accuracy with which it generates state vectors were analyzed. The ASR proved to be robust enough to process data with range and angle noise as large as 10,000 meters and 10(exp -6) radians together and 300,000 meters and 5x10(exp -4) radians separately at Lunar distances. The ASR was able to handle marginally more noise at distances closer to the Earth where the angle noise was less significant. The ASR is capable of effectively processing 40-80 data points gathered at a rate of one per 20 seconds at close Earth orbit and up to 28-40 data points gathered at a rate of one per minute at distant Earth orbit and Lunar orbit.

As high throughput screening (HTS) approaches play a larger role in toxicity testing, computational toxicology has emerged as a critical component in interpreting the large volume of data produced. Computational models for this purpose are becoming increasingly more sophisticated...

Health disparities in minorities and those of low socioeconomic status persist despite efforts to eliminate potential causes. Differences in the delivery of services can result in different healthcare outcomes and therefore, a health disparity. Some of this difference in care may attribute to discrimination resulting from clinical biases and…

Sleep-disordered breathing (SDB) is highly prevalent in heart failure (HF) patients. These breathing disturbances are independent predictors of increased morbidity and comorbid conditions that improve with SDB treatment. Considering the overlap between SDB-related and HF clinical symptoms reported by patients, objective tests need to be conducted for a diagnosis to be firmly established and to determine the type and severity of SDB that will dictate treatment alternatives. Considering the high success rate and diagnostic value of ambulatory monitoring techniques, they represent a practical, cost-effective, and accurate alternative to diagnosing SDB in HF patients.

Approximately 20% of all children in the United States live in poverty, which exists in rural, urban, and suburban areas. Thus, all child health clinicians need to be familiar with the effects of poverty on health and to understand associated, preventable, and modifiable social factors that impact health. Social determinants of health are identifiable root causes of medical problems. For children living in poverty, social determinants of health for which clinicians may play a role include the following: child maltreatment, child care and education, family financial support, physical environment, family social support, intimate partner violence, maternal depression and family mental illness, household substance abuse, firearm exposure, and parental health literacy. Children, particularly those living in poverty, exposed to adverse childhood experiences are susceptible to toxic stress and a variety of child and adult health problems, including developmental delay, asthma and heart disease. Despite the detrimental effects of social determinants on health, few child health clinicians routinely address the unmet social and psychosocial factors impacting children and their families during routine primary care visits. Clinicians need tools to screen for social determinants of health and to be familiar with available local and national resources to address these issues. These guidelines provide an overview of social determinants of health impacting children living in poverty and provide clinicians with practical screening tools and resources.

Data is organized into different data sets and includes descriptions of ToxCast chemicals and assays and files summarizing the screening results, a MySQL database, chemicals screened through Tox21, and available data generated from animal toxicity studies.

Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here, we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride.

SUMMARY Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch-reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride. PMID:25910244

This software consists of a set of application programs that support ground-based image processing for in situ missions. These programs represent a collection of utility routines that perform miscellaneous functions in the context of the ground data system. Each one fulfills some specific need as determined via operational experience. The most unique aspect to these programs is that they are integrated into the large, in situ image processing system via the PIG (Planetary Image Geometry) library. They work directly with space in situ data, understanding the appropriate image meta-data fields and updating them properly. The programs themselves are completely multimission; all mission dependencies are handled by PIG. This suite of programs consists of: (1)marscahv: Generates a linearized, epi-polar aligned image given a stereo pair of images. These images are optimized for 1-D stereo correlations, (2) marscheckcm: Compares the camera model in an image label with one derived via kinematics modeling on the ground, (3) marschkovl: Checks the overlaps between a list of images in order to determine which might be stereo pairs. This is useful for non-traditional stereo images like long-baseline or those from an articulating arm camera, (4) marscoordtrans: Translates mosaic coordinates from one form into another, (5) marsdispcompare: Checks a Left Right stereo disparity image against a Right Left disparity image to ensure they are consistent with each other, (6) marsdispwarp: Takes one image of a stereo pair and warps it through a disparity map to create a synthetic opposite- eye image. For example, a right eye image could be transformed to look like it was taken from the left eye via this program, (7) marsfidfinder: Finds fiducial markers in an image by projecting their approximate location and then using correlation to locate the markers to subpixel accuracy. These fiducial markets are small targets attached to the spacecraft surface. This helps verify, or improve, the

There is increasing pressure to provide cost-effective healthcare based on “best practice.” Consequently, new biomarkers are only likely to be introduced into routine clinical biochemistry departments if they are supported by a strong evidence base and if the results will improve patient management and outcome. This requires convincing evidence of the benefits of introducing the new test, ideally reflected in fewer hospital admissions, fewer additional investigations and/or fewer clinic visits. Carefully designed audit and cost-benefit studies in relevant patient groups must demonstrate that introducing the biomarker delivers an improved and more effective clinical pathway. From the laboratory perspective, pre-analytical requirements must be thoroughly investigated at an early stage. Good stability of the biomarker in relevant physiological matrices is essential to avoid the need for special processing. Absence of specific timing requirements for sampling and knowledge of the effect of medications that might be used to treat the patients in whom the biomarker will be measured is also highly desirable. Analytically, automation is essential in modern high-throughput clinical laboratories. Assays must therefore be robust, fulfilling standard requirements for linearity on dilution, precision and reproducibility, both within- and between-run. Provision of measurements by a limited number of specialized reference laboratories may be most appropriate, especially when a new biomarker is first introduced into routine practice. PMID:21137030

biological fluids with varying immunoreactivity which can present bioanalytical challenges when first discovered. The potential success of these efforts is greatly enhanced by recent advances in two closely linked technologies, toxicoproteomics and targeted, quantitative mass spectrometry. This review focuses on the examination of the current status of these technologies as they relate to the discovery and development of novel preclinical biomarkers of hepatotoxicity. A critical assessment of the current literature reveals two distinct lines of safety biomarker investigation, (1) peripheral fluid biomarkers of organ toxicity and (2) tissue or cell-based toxicity signatures. Improved peripheral fluid biomarkers should allow the sensitive detection of potential organ toxicity prior to the onset of overt organ pathology. Advancements in tissue or cell-based toxicity biomarkers will provide sensitive in vitro or ex vivo screening systems based on toxicity pathway markers. An examination of the current practices in clinical pathology and the critical evaluation of some recently proposed biomarker candidates in comparison to the desired characteristics of an ideal toxicity biomarker lead this author to conclude that a combination of selected biomarkers will be more informative if not predictive of potential animal organ toxicity than any single biomarker, new or old. For the practical assessment of combinations of conventional and/or novel toxicity biomarkers in rodent and large animal preclinical species, mass spectrometry has emerged as the premier analytical tool compared to specific immunoassays or functional assays. Selected and multiple reaction monitoring mass spectrometry applications make it possible for this same basic technology to be used in the progressive stages of biomarker discovery, development, and more importantly, routine study applications without the use of specific antibody reagents. This technology combined with other 'omics' technologies can provide added

Pesticide mixtures are common in streams with agricultural or urban influence in the watershed. The Pesticide Toxicity Index (PTI) is a screening tool to assess potential aquatic toxicity of complex pesticide mixtures by combining measures of pesticide exposure and acute toxicity in an additive toxic-unit model. The PTI is determined separately for fish, cladocerans, and benthic invertebrates. This study expands the number of pesticides and degradates included in previous editions of the PTI from 124 to 492 pesticides and degradates, and includes two types of PTI for use in different applications, depending on study objectives. The Median-PTI was calculated from median toxicity values for individual pesticides, so is robust to outliers and is appropriate for comparing relative potential toxicity among samples, sites, or pesticides. The Sensitive-PTI uses the 5th percentile of available toxicity values, so is a more sensitive screening-level indicator of potential toxicity. PTI predictions of toxicity in environmental samples were tested using data aggregated from published field studies that measured pesticide concentrations and toxicity to Ceriodaphnia dubia in ambient stream water. C. dubia survival was reduced to ≤50% of controls in 44% of samples with Median-PTI values of 0.1-1, and to 0% in 96% of samples with Median-PTI values >1. The PTI is a relative, but quantitative, indicator of potential toxicity that can be used to evaluate relationships between pesticide exposure and biological condition.

The rapid proliferation of many different engineered nanomaterials (defined as materials designed and produced to have structural features with at least one dimension of 100 nanometers or less) presents a dilemma to regulators regarding hazard identification. The International Life Sciences Institute Research Foundation/Risk Science Institute convened an expert working group to develop a screening strategy for the hazard identification of engineered nanomaterials. The working group report presents the elements of a screening strategy rather than a detailed testing protocol. Based on an evaluation of the limited data currently available, the report presents a broad data gathering strategy applicable to this early stage in the development of a risk assessment process for nanomaterials. Oral, dermal, inhalation, and injection routes of exposure are included recognizing that, depending on use patterns, exposure to nanomaterials may occur by any of these routes. The three key elements of the toxicityscreening strategy are: Physicochemical Characteristics, In Vitro Assays (cellular and non-cellular), and In Vivo Assays. There is a strong likelihood that biological activity of nanoparticles will depend on physicochemical parameters not routinely considered in toxicityscreening studies. Physicochemical properties that may be important in understanding the toxic effects of test materials include particle size and size distribution, agglomeration state, shape, crystal structure, chemical composition, surface area, surface chemistry, surface charge, and porosity. In vitro techniques allow specific biological and mechanistic pathways to be isolated and tested under controlled conditions, in ways that are not feasible in in vivo tests. Tests are suggested for portal-of-entry toxicity for lungs, skin, and the mucosal membranes, and target organ toxicity for endothelium, blood, spleen, liver, nervous system, heart, and kidney. Non-cellular assessment of nanoparticle durability

Diabetes mellitus is one of the most common diagnoses made by family physicians. Uncontrolled diabetes can lead to blindness, limb amputation, kidney failure, and vascular and heart disease. Screening patients before signs and symptoms develop leads to earlier diagnosis and treatment, but may not reduce rates of end-organ damage. Randomized trials show that screening for type 2 diabetes does not reduce mortality after 10 years, although some data suggest mortality benefits after 23 to 30 years. Lifestyle and pharmacologic interventions decrease progression to diabetes in patients with impaired fasting glucose or impaired glucose tolerance. Screening for type 1 diabetes is not recommended. The U.S. Preventive Services Task Force recommends screening for abnormal blood glucose and type 2 diabetes in adults 40 to 70 years of age who are overweight or obese, and repeating testing every three years if results are normal. Individuals at higher risk should be considered for earlier and more frequent screening. The American Diabetes Association recommends screening for type 2 diabetes annually in patients 45 years and older, or in patients younger than 45 years with major risk factors. The diagnosis can be made with a fasting plasma glucose level of 126 mg per dL or greater; an A1C level of 6.5% or greater; a random plasma glucose level of 200 mg per dL or greater; or a 75-g two-hour oral glucose tolerance test with a plasma glucose level of 200 mg per dL or greater. Results should be confirmed with repeat testing on a subsequent day; however, a single random plasma glucose level of 200 mg per dL or greater with typical signs and symptoms of hyperglycemia likely indicates diabetes. Additional testing to determine the etiology of diabetes is not routinely recommended.

FIO/RIO is a subroutine package that allows a FORTRAN programmer to access sequential and direct access data files in a machine independent manner. The package consists of stand alone FIO and RIO routines, which can be used independently of the Starlink software environment, plus routines to interface to the Starlink parameter system.

Children with complex disabilities such as autism spectrum disorders and Landau Kleffner syndrome often lack means to participate in everyday family routines. Serious problem behaviors may result from their challenges in responding to and initiating communicative interactions. These behaviors can change routine family activities such that the…

In order to understand how age and motor difficulties impact on daily routines, this qualitative investigation used focus groups and in-depth interviews with Australian and Canadian parents to examine the daily routines of younger (5 to 7 years of age) and older children (8 to 9 years of age) with and without Developmental Coordination Disorder…

PLOTAN, a generalized plot analysis routine written for the IBM 7094 computer, minimizes the difficulties in adding plot capabilities to large existing programs. PLOTAN is used in conjunction with a binary tape writing routine and has the ability to plot any variable on the intermediate binary tape as a function of any other.

The goal of this report is to describe the process by which new service practices in urban bureaucracies become routinized. The routinization process is studied by examining the life histories of six types of innovations: computer-assisted instruction; police computer systems; mobile intensive care units; closed circuit television systems; breath…

This study extends theory and research by differentiating between routine, noncreative performance and 2 distinct types of creativity: radical and incremental. We also use a sensemaking perspective to examine the interplay of social and personal factors that may influence a person's engagement in a certain level of creative action versus routine,…

This article describes thinking routines as tools to guide and support young children's thinking. These learning strategies, developed by Harvard University's Project Zero Classroom, actively engage students in constructing meaning while also understanding their own thinking process. The authors discuss how thinking routines can be used in both…

Routine activities theory has not fully considered the role of gender in shaping victimization and yet, the research literature clearly demonstrates that gender is associated with an individual's risk of victimization. In addition to the pervasive effect of gender on victimization, gender shapes an individual's daily routines and thus may create a…

This study examined the relationship between parental involvement routines and former Head Start children's literacy outcomes. Former Head Start children (n = 3, 808) from the National Head Start/Public School Transition Demonstration Research Project comprised the sample. Family routines and literacy outcomes in kindergarten were examined,…

The question of practical knowledge and its teaching has arisen more perceptibly since the appearance of the aim to professionalize teachers. How can imperceptible knowledge such as professional routines be taught? To establish a social fabric and effective class management, it is essential to call on creative and adaptive professional routines.…

See, Say, Write is an adaptable classroom writing routine that teachers can use across a range of activities in the preschool classroom. This preschool writing routine offers an opportunity for teachers to build on a shared experience through engagement in rich conversation and writing. After a shared experience, teachers will provide a visual…

Purpose: This paper presents routinized action theory as a way to examine the regular, habitual activities that occur in school organizations. Using this theoretical lens, school routines were analyzed in order to understand organizational stability and change. Design/methodology/approach: Using case study methods, three discrete cases are…